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Ensembl / ensembl-vep

The Ensembl Variant Effect Predictor predicts the functional effects of genomic variants
https://www.ensembl.org/vep
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gnomADe annotation not presented for a variant #1754

Open Aisha-D opened 1 month ago

Aisha-D commented 1 month ago

Describe the issue

A variant (X:15823107C>CAGCCGG) was not annotated using the gnomADe VCF provided (r2.1.1) by VEP b38. The gnomADe VCF has this variant present with AF=0.0147404 and so should have annotated the variant with the correct information :

chrX    15823107    rs752736259 C   CAGCCGG 3697473.05  PASS    AC=2495;AC_afr=566;AC_afr_female=464;AC_afr_male=102;AC_amr=168;AC_amr_female=139;AC_amr_male=29;AC_asj=339;AC_asj_female=256;AC_asj_male=83;AC_eas=11;AC_eas_female=10;AC_eas_jpn=0;AC_eas_kor=4;AC_eas_male=1;AC_eas_oea=7;AC_female=1882;AC_fin=382;AC_fin_female=271;AC_fin_male=111;AC_male=613;AC_nfe=904;AC_nfe_bgr=28;AC_nfe_est=1;AC_nfe_female=669;AC_nfe_male=235;AC_nfe_nwe=391;AC_nfe_onf=270;AC_nfe_seu=71;AC_nfe_swe=143;AC_oth=55;AC_oth_female=41;AC_oth_male=14;AC_popmax=566;AC_raw=3148;AC_sas=70;AC_sas_female=32;AC_sas_male=38;AF=1.47404e-02;AF_afr=5.26316e-02;AF_afr_female=5.58498e-02;AF_afr_male=4.17007e-02;AF_amr=6.32673e-03;AF_amr_female=6.94653e-03;AF_amr_male=4.43154e-03;AF_asj=4.80306e-02;AF_asj_female=5.44449e-02;AF_asj_male=3.52292e-02;AF_eas=8.35930e-04;AF_eas_female=1.09890e-03;AF_eas_jpn=0.00000e+00;AF_eas_kor=1.40154e-03;AF_eas_male=2.46366e-04;AF_eas_oea=6.84530e-04;AF_female=1.72111e-02;AF_fin=2.49624e-02;AF_fin_female=2.66104e-02;AF_fin_male=2.16839e-02;AF_male=1.02312e-02;AF_nfe=1.22568e-02;AF_nfe_bgr=1.57392e-02;AF_nfe_est=5.74713e-03;AF_nfe_female=1.43059e-02;AF_nfe_male=8.70661e-03;AF_nfe_nwe=1.36071e-02;AF_nfe_onf=1.33988e-02;AF_nfe_seu=1.25909e-02;AF_nfe_swe=8.27690e-03;AF_oth=1.29503e-02;AF_oth_female=1.46953e-02;AF_oth_male=9.60879e-03;AF_popmax=5.26316e-02;AF_raw=1.72382e-02;AF_sas=3.79754e-03;AF_sas_female=4.27236e-03;AF_sas_male=3.47254e-03;AN=169263;AN_afr=10754;AN_afr_female=8308;AN_afr_male=2446;AN_amr=26554;AN_amr_female=20010;AN_amr_male=6544;AN_asj=7058;AN_asj_female=4702;AN_asj_male=2356;AN_eas=13159;AN_eas_female=9100;AN_eas_jpn=79;AN_eas_kor=2854;AN_eas_male=4059;AN_eas_oea=10226;AN_female=109348;AN_fin=15303;AN_fin_female=10184;AN_fin_male=5119;AN_male=59915;AN_nfe=73755;AN_nfe_bgr=1779;AN_nfe_est=174;AN_nfe_female=46764;AN_nfe_male=26991;AN_nfe_nwe=28735;AN_nfe_onf=20151;AN_nfe_seu=5639;AN_nfe_swe=17277;AN_oth=4247;AN_oth_female=2790;AN_oth_male=1457;AN_popmax=10754;AN_raw=182618;AN_sas=18433;AN_sas_female=7490;AN_sas_male=10943;BaseQRankSum=3.61000e-01;ClippingRankSum=6.70000e-02;DP=5725913;FS=5.43000e-01;InbreedingCoeff=4.49800e-01;MQ=5.51700e+01;MQRankSum=-1.58900e+00;OriginalContig=X;OriginalStart=15841230;QD=2.35500e+01;ReadPosRankSum=-4.19000e-01;SOR=6.50000e-01;VQSLOD=1.36000e+00;VQSR_culprit=FS;ab_hist_alt_bin_freq=1|1|12|8|35|116|237|320|548|376|418|178|127|51|17|33|41|50|31|3;age_hist_het_bin_freq=51|60|102|109|133|125|128|99|86|65;age_hist_het_n_larger=37;age_hist_het_n_smaller=68;age_hist_hom_bin_freq=10|19|35|48|63|43|50|37|30|19;age_hist_hom_n_larger=8;age_hist_hom_n_smaller=13;allele_type=ins;controls_AC=1096;controls_AC_afr=265;controls_AC_afr_female=217;controls_AC_afr_male=48;controls_AC_amr=90;controls_AC_amr_female=76;controls_AC_amr_male=14;controls_AC_asj=67;controls_AC_asj_female=59;controls_AC_asj_male=8;controls_AC_eas=6;controls_AC_eas_female=6;controls_AC_eas_jpn=0;controls_AC_eas_kor=2;controls_AC_eas_male=0;controls_AC_eas_oea=4;controls_AC_female=838;controls_AC_fin=269;controls_AC_fin_female=186;controls_AC_fin_male=83;controls_AC_male=258;controls_AC_nfe=354;controls_AC_nfe_bgr=8;controls_AC_nfe_est=1;controls_AC_nfe_female=269;controls_AC_nfe_male=85;controls_AC_nfe_nwe=139;controls_AC_nfe_onf=107;controls_AC_nfe_seu=24;controls_AC_nfe_swe=75;controls_AC_oth=15;controls_AC_oth_female=11;controls_AC_oth_male=4;controls_AC_popmax=265;controls_AC_raw=1356;controls_AC_sas=30;controls_AC_sas_female=14;controls_AC_sas_male=16;controls_AF=1.45570e-02;controls_AF_afr=5.24960e-02;controls_AF_afr_female=5.56125e-02;controls_AF_afr_male=4.18848e-02;controls_AF_amr=6.81096e-03;controls_AF_amr_female=7.53819e-03;controls_AF_amr_male=4.46999e-03;controls_AF_asj=4.10791e-02;controls_AF_asj_female=5.17544e-02;controls_AF_asj_male=1.62933e-02;controls_AF_eas=9.34871e-04;controls_AF_eas_female=1.30095e-03;controls_AF_eas_jpn=0.00000e+00;controls_AF_eas_kor=1.38026e-03;controls_AF_eas_male=0.00000e+00;controls_AF_eas_oea=8.13835e-04;controls_AF_female=1.69368e-02;controls_AF_fin=2.81175e-02;controls_AF_fin_female=2.93283e-02;controls_AF_fin_male=2.57364e-02;controls_AF_male=9.99535e-03;controls_AF_nfe=1.24407e-02;controls_AF_nfe_bgr=1.74292e-02;controls_AF_nfe_est=2.17391e-02;controls_AF_nfe_female=1.47268e-02;controls_AF_nfe_male=8.34233e-03;controls_AF_nfe_nwe=1.36448e-02;controls_AF_nfe_onf=1.57631e-02;controls_AF_nfe_seu=1.07817e-02;controls_AF_nfe_swe=8.57241e-03;controls_AF_oth=1.08696e-02;controls_AF_oth_female=1.15304e-02;controls_AF_oth_male=9.38967e-03;controls_AF_popmax=5.24960e-02;controls_AF_raw=1.69250e-02;controls_AF_sas=3.13250e-03;controls_AF_sas_female=3.34928e-03;controls_AF_sas_male=2.96461e-03;controls_AN=75290;controls_AN_afr=5048;controls_AN_afr_female=3902;controls_AN_afr_male=1146;controls_AN_amr=13214;controls_AN_amr_female=10082;controls_AN_amr_male=3132;controls_AN_asj=1631;controls_AN_asj_female=1140;controls_AN_asj_male=491;controls_AN_eas=6418;controls_AN_eas_female=4612;controls_AN_eas_jpn=54;controls_AN_eas_kor=1449;controls_AN_eas_male=1806;controls_AN_eas_oea=4915;controls_AN_female=49478;controls_AN_fin=9567;controls_AN_fin_female=6342;controls_AN_fin_male=3225;controls_AN_male=25812;controls_AN_nfe=28455;controls_AN_nfe_bgr=459;controls_AN_nfe_est=46;controls_AN_nfe_female=18266;controls_AN_nfe_male=10189;controls_AN_nfe_nwe=10187;controls_AN_nfe_onf=6788;controls_AN_nfe_seu=2226;controls_AN_nfe_swe=8749;controls_AN_oth=1380;controls_AN_oth_female=954;controls_AN_oth_male=426;controls_AN_popmax=5048;controls_AN_raw=80118;controls_AN_sas=9577;controls_AN_sas_female=4180;controls_AN_sas_male=5397;controls_nhomalt=13;controls_nhomalt_afr=4;controls_nhomalt_afr_female=4;controls_nhomalt_afr_male=0;controls_nhomalt_amr=1;controls_nhomalt_amr_female=1;controls_nhomalt_amr_male=0;controls_nhomalt_asj=3;controls_nhomalt_asj_female=3;controls_nhomalt_asj_male=0;controls_nhomalt_eas=0;controls_nhomalt_eas_female=0;controls_nhomalt_eas_jpn=0;controls_nhomalt_eas_kor=0;controls_nhomalt_eas_male=0;controls_nhomalt_eas_oea=0;controls_nhomalt_female=13;controls_nhomalt_fin=3;controls_nhomalt_fin_female=3;controls_nhomalt_fin_male=0;controls_nhomalt_male=0;controls_nhomalt_nfe=2;controls_nhomalt_nfe_bgr=0;controls_nhomalt_nfe_est=0;controls_nhomalt_nfe_female=2;controls_nhomalt_nfe_male=0;controls_nhomalt_nfe_nwe=1;controls_nhomalt_nfe_onf=1;controls_nhomalt_nfe_seu=0;controls_nhomalt_nfe_swe=0;controls_nhomalt_oth=0;controls_nhomalt_oth_female=0;controls_nhomalt_oth_male=0;controls_nhomalt_popmax=4;controls_nhomalt_raw=20;controls_nhomalt_sas=0;controls_nhomalt_sas_female=0;controls_nhomalt_sas_male=0;controls_popmax=afr;dp_hist_all_bin_freq=5541|11272|17213|19476|19779|15658|16569|27393|18172|6668|2565|1301|778|509|326|248|214|109|113|96;dp_hist_all_n_larger=331;dp_hist_alt_bin_freq=249|646|631|546|356|285|213|145|113|86|105|105|125|90|87|50|41|21|20|15;dp_hist_alt_n_larger=79;faf95=1.42582e-02;faf95_afr=4.90456e-02;faf95_amr=5.54570e-03;faf95_eas=4.68540e-04;faf95_nfe=1.15939e-02;faf95_sas=3.08274e-03;faf99=1.42575e-02;faf99_afr=4.90457e-02;faf99_amr=5.54547e-03;faf99_eas=4.68720e-04;faf99_nfe=1.15934e-02;faf99_sas=3.08262e-03;gq_hist_all_bin_freq=2637|4114|2531|5426|6806|3945|8248|8748|4623|8459|8219|4214|10294|4148|5388|4429|6651|1902|5844|56564;gq_hist_alt_bin_freq=12|91|109|132|180|118|104|123|99|69|74|66|45|37|24|39|37|26|33|2590;n_alt_alleles=6;nhomalt=32;nhomalt_afr=13;nhomalt_afr_female=13;nhomalt_afr_male=0;nhomalt_amr=1;nhomalt_amr_female=1;nhomalt_amr_male=0;nhomalt_asj=6;nhomalt_asj_female=6;nhomalt_asj_male=0;nhomalt_eas=0;nhomalt_eas_female=0;nhomalt_eas_jpn=0;nhomalt_eas_kor=0;nhomalt_eas_male=0;nhomalt_eas_oea=0;nhomalt_female=32;nhomalt_fin=6;nhomalt_fin_female=6;nhomalt_fin_male=0;nhomalt_male=0;nhomalt_nfe=6;nhomalt_nfe_bgr=1;nhomalt_nfe_est=0;nhomalt_nfe_female=6;nhomalt_nfe_male=0;nhomalt_nfe_nwe=2;nhomalt_nfe_onf=1;nhomalt_nfe_seu=0;nhomalt_nfe_swe=2;nhomalt_oth=0;nhomalt_oth_female=0;nhomalt_oth_male=0;nhomalt_popmax=13;nhomalt_raw=54;nhomalt_sas=0;nhomalt_sas_female=0;nhomalt_sas_male=0;non_cancer_AC=2379;non_cancer_AC_afr=524;non_cancer_AC_afr_female=427;non_cancer_AC_afr_male=97;non_cancer_AC_amr=166;non_cancer_AC_amr_female=137;non_cancer_AC_amr_male=29;non_cancer_AC_asj=332;non_cancer_AC_asj_female=249;non_cancer_AC_asj_male=83;non_cancer_AC_eas=11;non_cancer_AC_eas_female=10;non_cancer_AC_eas_jpn=0;non_cancer_AC_eas_kor=4;non_cancer_AC_eas_male=1;non_cancer_AC_eas_oea=7;non_cancer_AC_female=1785;non_cancer_AC_fin=382;non_cancer_AC_fin_female=271;non_cancer_AC_fin_male=111;non_cancer_AC_male=594;non_cancer_AC_nfe=843;non_cancer_AC_nfe_bgr=28;non_cancer_AC_nfe_est=1;non_cancer_AC_nfe_female=620;non_cancer_AC_nfe_male=223;non_cancer_AC_nfe_nwe=376;non_cancer_AC_nfe_onf=242;non_cancer_AC_nfe_seu=60;non_cancer_AC_nfe_swe=136;non_cancer_AC_oth=51;non_cancer_AC_oth_female=39;non_cancer_AC_oth_male=12;non_cancer_AC_popmax=524;non_cancer_AC_raw=2940;non_cancer_AC_sas=70;non_cancer_AC_sas_female=32;non_cancer_AC_sas_male=38;non_cancer_AF=1.48767e-02;non_cancer_AF_afr=5.33279e-02;non_cancer_AF_afr_female=5.64815e-02;non_cancer_AF_afr_male=4.28067e-02;non_cancer_AF_amr=6.30292e-03;non_cancer_AF_amr_female=6.90315e-03;non_cancer_AF_amr_male=4.46772e-03;non_cancer_AF_asj=4.93240e-02;non_cancer_AF_asj_female=5.60558e-02;non_cancer_AF_asj_male=3.62604e-02;non_cancer_AF_eas=8.66278e-04;non_cancer_AF_eas_female=1.14155e-03;non_cancer_AF_eas_jpn=0.00000e+00;non_cancer_AF_eas_kor=1.41443e-03;non_cancer_AF_eas_male=2.53936e-04;non_cancer_AF_eas_oea=7.13630e-04;non_cancer_AF_female=1.74225e-02;non_cancer_AF_fin=2.49836e-02;non_cancer_AF_fin_female=2.66418e-02;non_cancer_AF_fin_male=2.16882e-02;non_cancer_AF_male=1.03374e-02;non_cancer_AF_nfe=1.26324e-02;non_cancer_AF_nfe_bgr=1.65192e-02;non_cancer_AF_nfe_est=8.84956e-03;non_cancer_AF_nfe_female=1.48838e-02;non_cancer_AF_nfe_male=8.89261e-03;non_cancer_AF_nfe_nwe=1.39803e-02;non_cancer_AF_nfe_onf=1.49503e-02;non_cancer_AF_nfe_seu=1.18087e-02;non_cancer_AF_nfe_swe=8.11359e-03;non_cancer_AF_oth=1.29870e-02;non_cancer_AF_oth_female=1.51633e-02;non_cancer_AF_oth_male=8.85609e-03;non_cancer_AF_popmax=5.33279e-02;non_cancer_AF_raw=1.71456e-02;non_cancer_AF_sas=3.80994e-03;non_cancer_AF_sas_female=4.29761e-03;non_cancer_AF_sas_male=3.47762e-03;non_cancer_AN=159915;non_cancer_AN_afr=9826;non_cancer_AN_afr_female=7560;non_cancer_AN_afr_male=2266;non_cancer_AN_amr=26337;non_cancer_AN_amr_female=19846;non_cancer_AN_amr_male=6491;non_cancer_AN_asj=6731;non_cancer_AN_asj_female=4442;non_cancer_AN_asj_male=2289;non_cancer_AN_eas=12698;non_cancer_AN_eas_female=8760;non_cancer_AN_eas_jpn=61;non_cancer_AN_eas_kor=2828;non_cancer_AN_eas_male=3938;non_cancer_AN_eas_oea=9809;non_cancer_AN_female=102454;non_cancer_AN_fin=15290;non_cancer_AN_fin_female=10172;non_cancer_AN_fin_male=5118;non_cancer_AN_male=57461;non_cancer_AN_nfe=66733;non_cancer_AN_nfe_bgr=1695;non_cancer_AN_nfe_est=113;non_cancer_AN_nfe_female=41656;non_cancer_AN_nfe_male=25077;non_cancer_AN_nfe_nwe=26895;non_cancer_AN_nfe_onf=16187;non_cancer_AN_nfe_seu=5081;non_cancer_AN_nfe_swe=16762;non_cancer_AN_oth=3927;non_cancer_AN_oth_female=2572;non_cancer_AN_oth_male=1355;non_cancer_AN_popmax=9826;non_cancer_AN_raw=171473;non_cancer_AN_sas=18373;non_cancer_AN_sas_female=7446;non_cancer_AN_sas_male=10927;non_cancer_nhomalt=31;non_cancer_nhomalt_afr=12;non_cancer_nhomalt_afr_female=12;non_cancer_nhomalt_afr_male=0;non_cancer_nhomalt_amr=1;non_cancer_nhomalt_amr_female=1;non_cancer_nhomalt_amr_male=0;non_cancer_nhomalt_asj=6;non_cancer_nhomalt_asj_female=6;non_cancer_nhomalt_asj_male=0;non_cancer_nhomalt_eas=0;non_cancer_nhomalt_eas_female=0;non_cancer_nhomalt_eas_jpn=0;non_cancer_nhomalt_eas_kor=0;non_cancer_nhomalt_eas_male=0;non_cancer_nhomalt_eas_oea=0;non_cancer_nhomalt_female=31;non_cancer_nhomalt_fin=6;non_cancer_nhomalt_fin_female=6;non_cancer_nhomalt_fin_male=0;non_cancer_nhomalt_male=0;non_cancer_nhomalt_nfe=6;non_cancer_nhomalt_nfe_bgr=1;non_cancer_nhomalt_nfe_est=0;non_cancer_nhomalt_nfe_female=6;non_cancer_nhomalt_nfe_male=0;non_cancer_nhomalt_nfe_nwe=2;non_cancer_nhomalt_nfe_onf=1;non_cancer_nhomalt_nfe_seu=0;non_cancer_nhomalt_nfe_swe=2;non_cancer_nhomalt_oth=0;non_cancer_nhomalt_oth_female=0;non_cancer_nhomalt_oth_male=0;non_cancer_nhomalt_popmax=12;non_cancer_nhomalt_raw=47;non_cancer_nhomalt_sas=0;non_cancer_nhomalt_sas_female=0;non_cancer_nhomalt_sas_male=0;non_cancer_popmax=afr;non_neuro_AC=2054;non_neuro_AC_afr=565;non_neuro_AC_afr_female=463;non_neuro_AC_afr_male=102;non_neuro_AC_amr=136;non_neuro_AC_amr_female=114;non_neuro_AC_amr_male=22;non_neuro_AC_asj=204;non_neuro_AC_asj_female=164;non_neuro_AC_asj_male=40;non_neuro_AC_eas=10;non_neuro_AC_eas_female=9;non_neuro_AC_eas_jpn=0;non_neuro_AC_eas_kor=4;non_neuro_AC_eas_male=1;non_neuro_AC_eas_oea=6;non_neuro_AC_female=1561;non_neuro_AC_fin=302;non_neuro_AC_fin_female=206;non_neuro_AC_fin_male=96;non_neuro_AC_male=493;non_neuro_AC_nfe=728;non_neuro_AC_nfe_bgr=3;non_neuro_AC_nfe_est=1;non_neuro_AC_nfe_female=544;non_neuro_AC_nfe_male=184;non_neuro_AC_nfe_nwe=331;non_neuro_AC_nfe_onf=236;non_neuro_AC_nfe_seu=63;non_neuro_AC_nfe_swe=94;non_neuro_AC_oth=39;non_neuro_AC_oth_female=29;non_neuro_AC_oth_male=10;non_neuro_AC_popmax=565;non_neuro_AC_raw=2598;non_neuro_AC_sas=70;non_neuro_AC_sas_female=32;non_neuro_AC_sas_male=38;non_neuro_AF=1.46962e-02;non_neuro_AF_afr=5.26610e-02;non_neuro_AF_afr_female=5.58370e-02;non_neuro_AF_afr_male=4.18547e-02;non_neuro_AF_amr=5.77814e-03;non_neuro_AF_amr_female=6.33122e-03;non_neuro_AF_amr_male=3.97758e-03;non_neuro_AF_asj=4.74639e-02;non_neuro_AF_asj_female=5.64738e-02;non_neuro_AF_asj_male=2.86944e-02;non_neuro_AF_eas=1.02987e-03;non_neuro_AF_eas_female=1.35095e-03;non_neuro_AF_eas_jpn=0.00000e+00;non_neuro_AF_eas_kor=1.40252e-03;non_neuro_AF_eas_male=3.28084e-04;non_neuro_AF_eas_oea=8.85086e-04;non_neuro_AF_female=1.73433e-02;non_neuro_AF_fin=2.59763e-02;non_neuro_AF_fin_female=2.74740e-02;non_neuro_AF_fin_male=2.32558e-02;non_neuro_AF_male=9.90795e-03;non_neuro_AF_nfe=1.25405e-02;non_neuro_AF_nfe_bgr=1.03806e-02;non_neuro_AF_nfe_est=6.41026e-03;non_neuro_AF_nfe_female=1.47457e-02;non_neuro_AF_nfe_male=8.69565e-03;non_neuro_AF_nfe_nwe=1.36698e-02;non_neuro_AF_nfe_onf=1.30372e-02;non_neuro_AF_nfe_seu=1.18488e-02;non_neuro_AF_nfe_swe=9.42450e-03;non_neuro_AF_oth=1.15248e-02;non_neuro_AF_oth_female=1.28092e-02;non_neuro_AF_oth_male=8.92857e-03;non_neuro_AF_popmax=5.26610e-02;non_neuro_AF_raw=1.71986e-02;non_neuro_AF_sas=3.79857e-03;non_neuro_AF_sas_female=4.27350e-03;non_neuro_AF_sas_male=3.47349e-03;non_neuro_AN=139764;non_neuro_AN_afr=10729;non_neuro_AN_afr_female=8292;non_neuro_AN_afr_male=2437;non_neuro_AN_amr=23537;non_neuro_AN_amr_female=18006;non_neuro_AN_amr_male=5531;non_neuro_AN_asj=4298;non_neuro_AN_asj_female=2904;non_neuro_AN_asj_male=1394;non_neuro_AN_eas=9710;non_neuro_AN_eas_female=6662;non_neuro_AN_eas_jpn=79;non_neuro_AN_eas_kor=2852;non_neuro_AN_eas_male=3048;non_neuro_AN_eas_oea=6779;non_neuro_AN_female=90006;non_neuro_AN_fin=11626;non_neuro_AN_fin_female=7498;non_neuro_AN_fin_male=4128;non_neuro_AN_male=49758;non_neuro_AN_nfe=58052;non_neuro_AN_nfe_bgr=289;non_neuro_AN_nfe_est=156;non_neuro_AN_nfe_female=36892;non_neuro_AN_nfe_male=21160;non_neuro_AN_nfe_nwe=24214;non_neuro_AN_nfe_onf=18102;non_neuro_AN_nfe_seu=5317;non_neuro_AN_nfe_swe=9974;non_neuro_AN_oth=3384;non_neuro_AN_oth_female=2264;non_neuro_AN_oth_male=1120;non_neuro_AN_popmax=10729;non_neuro_AN_raw=151059;non_neuro_AN_sas=18428;non_neuro_AN_sas_female=7488;non_neuro_AN_sas_male=10940;non_neuro_faf95=1.38409e-02;non_neuro_faf95_afr=4.73059e-02;non_neuro_faf95_amr=5.67405e-03;non_neuro_faf95_eas=4.06800e-04;non_neuro_faf95_nfe=1.13728e-02;non_neuro_faf95_sas=2.25409e-03;non_neuro_faf99=1.38412e-02;non_neuro_faf99_afr=4.73059e-02;non_neuro_faf99_amr=5.67391e-03;non_neuro_faf99_eas=4.06860e-04;non_neuro_faf99_nfe=1.13729e-02;non_neuro_faf99_sas=2.25438e-03;non_neuro_nhomalt=25;non_neuro_nhomalt_afr=13;non_neuro_nhomalt_afr_female=13;non_neuro_nhomalt_afr_male=0;non_neuro_nhomalt_amr=1;non_neuro_nhomalt_amr_female=1;non_neuro_nhomalt_amr_male=0;non_neuro_nhomalt_asj=5;non_neuro_nhomalt_asj_female=5;non_neuro_nhomalt_asj_male=0;non_neuro_nhomalt_eas=0;non_neuro_nhomalt_eas_female=0;non_neuro_nhomalt_eas_jpn=0;non_neuro_nhomalt_eas_kor=0;non_neuro_nhomalt_eas_male=0;non_neuro_nhomalt_eas_oea=0;non_neuro_nhomalt_female=25;non_neuro_nhomalt_fin=4;non_neuro_nhomalt_fin_female=4;non_neuro_nhomalt_fin_male=0;non_neuro_nhomalt_male=0;non_neuro_nhomalt_nfe=2;non_neuro_nhomalt_nfe_bgr=0;non_neuro_nhomalt_nfe_est=0;non_neuro_nhomalt_nfe_female=2;non_neuro_nhomalt_nfe_male=0;non_neuro_nhomalt_nfe_nwe=1;non_neuro_nhomalt_nfe_onf=1;non_neuro_nhomalt_nfe_seu=0;non_neuro_nhomalt_nfe_swe=0;non_neuro_nhomalt_oth=0;non_neuro_nhomalt_oth_female=0;non_neuro_nhomalt_oth_male=0;non_neuro_nhomalt_popmax=13;non_neuro_nhomalt_raw=45;non_neuro_nhomalt_sas=0;non_neuro_nhomalt_sas_female=0;non_neuro_nhomalt_sas_male=0;non_neuro_popmax=afr;non_topmed_AC=2356;non_topmed_AC_afr=449;non_topmed_AC_afr_female=355;non_topmed_AC_afr_male=94;non_topmed_AC_amr=166;non_topmed_AC_amr_female=137;non_topmed_AC_amr_male=29;non_topmed_AC_asj=337;non_topmed_AC_asj_female=256;non_topmed_AC_asj_male=81;non_topmed_AC_eas=11;non_topmed_AC_eas_female=10;non_topmed_AC_eas_jpn=0;non_topmed_AC_eas_kor=4;non_topmed_AC_eas_male=1;non_topmed_AC_eas_oea=7;non_topmed_AC_female=1756;non_topmed_AC_fin=382;non_topmed_AC_fin_female=271;non_topmed_AC_fin_male=111;non_topmed_AC_male=600;non_topmed_AC_nfe=886;non_topmed_AC_nfe_bgr=28;non_topmed_AC_nfe_est=1;non_topmed_AC_nfe_female=654;non_topmed_AC_nfe_male=232;non_topmed_AC_nfe_nwe=379;non_topmed_AC_nfe_onf=264;non_topmed_AC_nfe_seu=71;non_topmed_AC_nfe_swe=143;non_topmed_AC_oth=55;non_topmed_AC_oth_female=41;non_topmed_AC_oth_male=14;non_topmed_AC_popmax=449;non_topmed_AC_raw=2955;non_topmed_AC_sas=70;non_topmed_AC_sas_female=32;non_topmed_AC_sas_male=38;non_topmed_AF=1.42543e-02;non_topmed_AF_afr=5.59781e-02;non_topmed_AF_afr_female=5.86196e-02;non_topmed_AF_afr_male=4.78372e-02;non_topmed_AF_amr=6.27552e-03;non_topmed_AF_amr_female=6.87268e-03;non_topmed_AF_amr_male=4.44922e-03;non_topmed_AF_asj=4.80125e-02;non_topmed_AF_asj_female=5.47711e-02;non_topmed_AF_asj_male=3.45416e-02;non_topmed_AF_eas=8.36057e-04;non_topmed_AF_eas_female=1.09890e-03;non_topmed_AF_eas_jpn=0.00000e+00;non_topmed_AF_eas_kor=1.40154e-03;non_topmed_AF_eas_male=2.46488e-04;non_topmed_AF_eas_oea=6.84664e-04;non_topmed_AF_female=1.65426e-02;non_topmed_AF_fin=2.49657e-02;non_topmed_AF_fin_female=2.66156e-02;non_topmed_AF_fin_male=2.16839e-02;non_topmed_AF_male=1.01466e-02;non_topmed_AF_nfe=1.21866e-02;non_topmed_AF_nfe_bgr=1.57392e-02;non_topmed_AF_nfe_est=5.84795e-03;non_topmed_AF_nfe_female=1.42291e-02;non_topmed_AF_nfe_male=8.67582e-03;non_topmed_AF_nfe_nwe=1.34909e-02;non_topmed_AF_nfe_onf=1.33509e-02;non_topmed_AF_nfe_seu=1.26245e-02;non_topmed_AF_nfe_swe=8.28409e-03;non_topmed_AF_oth=1.31046e-02;non_topmed_AF_oth_female=1.48983e-02;non_topmed_AF_oth_male=9.68858e-03;non_topmed_AF_popmax=5.59781e-02;non_topmed_AF_raw=1.66616e-02;non_topmed_AF_sas=3.79754e-03;non_topmed_AF_sas_female=4.27236e-03;non_topmed_AF_sas_male=3.47254e-03;non_topmed_AN=165283;non_topmed_AN_afr=8021;non_topmed_AN_afr_female=6056;non_topmed_AN_afr_male=1965;non_topmed_AN_amr=26452;non_topmed_AN_amr_female=19934;non_topmed_AN_amr_male=6518;non_topmed_AN_asj=7019;non_topmed_AN_asj_female=4674;non_topmed_AN_asj_male=2345;non_topmed_AN_eas=13157;non_topmed_AN_eas_female=9100;non_topmed_AN_eas_jpn=79;non_topmed_AN_eas_kor=2854;non_topmed_AN_eas_male=4057;non_topmed_AN_eas_oea=10224;non_topmed_AN_female=106150;non_topmed_AN_fin=15301;non_topmed_AN_fin_female=10182;non_topmed_AN_fin_male=5119;non_topmed_AN_male=59133;non_topmed_AN_nfe=72703;non_topmed_AN_nfe_bgr=1779;non_topmed_AN_nfe_est=171;non_topmed_AN_nfe_female=45962;non_topmed_AN_nfe_male=26741;non_topmed_AN_nfe_nwe=28093;non_topmed_AN_nfe_onf=19774;non_topmed_AN_nfe_seu=5624;non_topmed_AN_nfe_swe=17262;non_topmed_AN_oth=4197;non_topmed_AN_oth_female=2752;non_topmed_AN_oth_male=1445;non_topmed_AN_popmax=8021;non_topmed_AN_raw=177354;non_topmed_AN_sas=18433;non_topmed_AN_sas_female=7490;non_topmed_AN_sas_male=10943;non_topmed_nhomalt=30;non_topmed_nhomalt_afr=11;non_topmed_nhomalt_afr_female=11;non_topmed_nhomalt_afr_male=0;non_topmed_nhomalt_amr=1;non_topmed_nhomalt_amr_female=1;non_topmed_nhomalt_amr_male=0;non_topmed_nhomalt_asj=6;non_topmed_nhomalt_asj_female=6;non_topmed_nhomalt_asj_male=0;non_topmed_nhomalt_eas=0;non_topmed_nhomalt_eas_female=0;non_topmed_nhomalt_eas_jpn=0;non_topmed_nhomalt_eas_kor=0;non_topmed_nhomalt_eas_male=0;non_topmed_nhomalt_eas_oea=0;non_topmed_nhomalt_female=30;non_topmed_nhomalt_fin=6;non_topmed_nhomalt_fin_female=6;non_topmed_nhomalt_fin_male=0;non_topmed_nhomalt_male=0;non_topmed_nhomalt_nfe=6;non_topmed_nhomalt_nfe_bgr=1;non_topmed_nhomalt_nfe_est=0;non_topmed_nhomalt_nfe_female=6;non_topmed_nhomalt_nfe_male=0;non_topmed_nhomalt_nfe_nwe=2;non_topmed_nhomalt_nfe_onf=1;non_topmed_nhomalt_nfe_seu=0;non_topmed_nhomalt_nfe_swe=2;non_topmed_nhomalt_oth=0;non_topmed_nhomalt_oth_female=0;non_topmed_nhomalt_oth_male=0;non_topmed_nhomalt_popmax=11;non_topmed_nhomalt_raw=49;non_topmed_nhomalt_sas=0;non_topmed_nhomalt_sas_female=0;non_topmed_nhomalt_sas_male=0;non_topmed_popmax=afr;nonpar;pab_max=1.00000e+00;popmax=afr;rf_tp_probability=7.84117e-01;segdup;variant_type=mixed;vep=AGCCGG|inframe_insertion|MODERATE|ZRSR2|ENSG00000169249|Transcript|ENST00000307771|protein_coding|11/11||ENST00000307771.7:c.1338_1343dupGAGCCG|ENSP00000303015.7:p.Ser447_Arg448dup|1338-1339|1314-1315|438-439|-/SR|-/AGCCGG|rs752736259|1||1||insertion|1|HGNC|23019|YES|||CCDS14172.1|ENSP00000303015|Q15696||UPI0000137929||||Low_complexity_(Seg):seg&hmmpanther:PTHR12620:SF6&hmmpanther:PTHR12620|29|AGCCGG:0.0236||AGCCGG:0.0492|AGCCGG:0.0086|AGCCGG:0|AGCCGG:0.0159|AGCCGG:0.002||||||||||||||||||||||,AGCCGG|downstream_gene_variant|MODIFIER|AP1S2|ENSG00000182287|Transcript|ENST00000329235|protein_coding||||||||||rs752736259|1|2698|-1||insertion|1|HGNC|560|YES|||CCDS14173.1|ENSP00000328789|P56377|Q549M9|UPI0000124FEC|1|||||AGCCGG:0.0236||AGCCGG:0.0492|AGCCGG:0.0086|AGCCGG:0|AGCCGG:0.0159|AGCCGG:0.002||||||||||||||||||||||,AGCCGG|downstream_gene_variant|MODIFIER|AP1S2|ENSG00000182287|Transcript|ENST00000452376|protein_coding||||||||||rs752736259|1|3784|-1|cds_start_NF|insertion|1|HGNC|560|||||ENSP00000403498|||UPI000059DAD2|1|||||AGCCGG:0.0236||AGCCGG:0.0492|AGCCGG:0.0086|AGCCGG:0|AGCCGG:0.0159|AGCCGG:0.002||||||||||||||||||||||;was_mixed

I have run this variant using the cache but the same output was observed where this variant was not annotated. The gnomad r2.1.1 was used. The command was:

docker run -v /home/dnanexus:/opt/vep/.vep ensemblorg/ensembl-vep:release_103.1 ./vep -i /opt/vep/.vep/130_split.vcf -o /opt/vep/.vep/130_split_filevep.vcf --vcf --cache --refseq --exclude_predicted --symbol --hgvs --af_gnomad --check_existing --variant_class --numbers --offline --custom /opt/vep/.vep/clinvar_20240611_GRCh38.vcf.gz,ClinVar,vcf,exact,0,CLNSIG,CLNREVSTAT,CLNDN --custom /opt/vep/.vep/h_samples_withoutchr.vcf.gz,Prev,vcf,exact,0,AC,NS --custom /opt/vep/.vep/CosmicCodingMuts_GRCh38_v99.normal.vcf.gz,COSMIC,vcf,exact,0,ID --custom /opt/vep/.vep/CosmicNonCodingVariants_GRCh38_v99.normal.vcf.gz,COSMIC,vcf,exact,0,ID --plugin CADD,/opt/vep/.vep/./whole_genome_SNVs.tsv.gz,/opt/vep/.vep/./gnomad.genomes.r3.0.indel.tsv.gz --fields SYMBOL,VARIANT_CLASS,Consequence,EXON,HGVSc,HGVSp,gnomAD_AF,CADD_PHRED,Existing_variation,ClinVar,ClinVar_CLNDN,ClinVar_CLNSIG,COSMIC,Prev_AC,Prev_NS,Feature --fork 4 --no_stats

I also tested using the online VEP to see if this would not be annotated by VEP but found that the variant was annotated correctly, I have attached the output of this VEP job: vep_online.txt

I am aware that the online is a more recent version of vep 112 but I want to understand what caused this variant to not be annotated by gnomADe correctly.

System

dglemos commented 1 month ago

Hi @Aisha-D, Can you please run vep with the minimal options, something like this:

docker run -v /home/dnanexus:/opt/vep/.vep ensemblorg/ensembl-vep:release_103.1 ./vep \
-i /opt/vep/.vep/variant.vcf \
-o /opt/vep/.vep/output.txt \
--offline \
--cache_version 103 \
--refseq \
--af_gnomad

variant.vcf containing only: chrX 15823107 . C CAGCCGG . . .

Aisha-D commented 1 month ago

Hi,

I have run this locally and it does not produce any gnomAD annotations. Below is my command:

sudo docker run  -v /home/dnanexus:/opt/vep/.vep ensemblorg/ensembl-vep:release_103.1  ./vep -i /opt/vep/.vep/variant.vcf -o /opt/vep/.vep/out.vcf --offline --cache_version 103 --refseq --af_gnomad --use_given_ref --force

The results:

$ grep -v ^"#" out.vcf
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8905    NM_001272071.2  Transcript      downstream_gene_variant -       -       -       -       -       -       IMPACT=MODIFIER;DISTANCE=2698;STRAND=-1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8905    NM_003916.5     Transcript      downstream_gene_variant -       -       -       -       -       -       IMPACT=MODIFIER;DISTANCE=2698;STRAND=-1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    NM_005089.4     Transcript      inframe_insertion       1326-1327       1314-1315       438-439 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_005274597.3  Transcript      inframe_insertion       1327-1328       900-901 300-301 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_011545589.3  Transcript      inframe_insertion       1291-1292       1236-1237       412-413 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_017029881.2  Transcript      inframe_insertion       1326-1327       1314-1315       438-439 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_017029882.2  Transcript      inframe_insertion       1281-1282       900-901 300-301 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_017029883.2  Transcript      inframe_insertion       1422-1423       900-901 300-301 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_024452455.1  Transcript      inframe_insertion       1450-1451       900-901 300-301 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8233    XM_024452456.1  Transcript      inframe_insertion       1475-1476       900-901 300-301 -/SR    -/AGCCGG        -       IMPACT=MODERATE;STRAND=1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8905    XR_002958809.1  Transcript      downstream_gene_variant -       -       -       -       -       -       IMPACT=MODIFIER;DISTANCE=2700;STRAND=-1
X_15823108_-/AGCCGG     X:15823107-15823108     AGCCGG  8905    XR_247289.3     Transcript      downstream_gene_variant -       -       -       -       -       -       IMPACT=MODIFIER;DISTANCE=2700;STRAND=-1

There was no gnomad annotation to this variant.

Aisha-D commented 3 weeks ago

Hi @dglemos

We managed to sort this by changing the VEP docker cache to be the indexed cache. The non-index cache was causing this issue. It seemed to affect specific insertion variants, do you know why this may have been the case?

Many thanks, Aisha

dglemos commented 3 weeks ago

Thank you @Aisha-D I can now reproduce the issue. The problem is in the non-indexed cache, not in your input variants. We recommend all users to work exclusively with indexed caches, we are going to update the documentation and the FTP to clarify what caches should be used.

Best wishes, Diana