Issue: Missing Plugin Columns in INFO Field of VCF File when Using dbNSFP with VEP

[poddarharsh15]

Hello everyone,

I am running the annotation step using VEP with the "dbNSFP" plugin. I tried running dbNSFP with ALL filters and specified the parameters I needed, but I am not seeing all the plugin columns in the INFO field of the VCF file. Could you please suggest some ideas?

Thank you.

I need below mention scores CADD_raw,CADD_raw_rankscore,CADD_phred,Polyphen2_HDIV_score,Polyphen2_HDIV_rankscore,Polyphen2_HDIV_pred,Polyphen2_HVAR_score,Polyphen2_HVAR_rankscore,Polyphen2_HVAR_pred,gnomAD_exomes_flag,gnomAD_exomes_AC,gnomAD_exomes_AN,gnomAD_exomes_AF,gnomAD_exomes_nhomalt,gnomAD_exomes_ASJ_AC,gnomAD_exomes_ASJ_AN,gnomAD_exomes_ASJ_AF,AlphaMissense_pred,AlphaMissense_rankscore,AlphaMissense_score,SIFT_score,SIFT_pred,SIFT_converted_rankscore,SIFT4G_score,SIFT4G_converted_rankscore,SIFT4G_pred,EVE_score,ESM1b_rankscore,ESM1b_pred,ESM1b_score,EVE_Class10_pred,SORVA_LOF_MAF0.005_HetOrHom,REVEL_score,REVEL_rankscore,MetaRNN_score,MetaRNN_phred,MetaRNN_rankscore

version used==dbNSFP4.8a_grch38.gz

vep \
    -i AshkenazimTrio_WES_P.vcf.gz \
    -o AshkenazimTrio_WES_P.VEP.ann.vcf.gz \
    --stats_file AshkenazimTrio_WES_P.manta.diploid_sv_VEP.ann.summary.html --plugin dbNSFP,dbNSFP4.8a_grch38.gz,ALL  --plugin LoF,loftee_path:/usr/local/share/ensembl-vep-112 --plugin>
    --compress_output bgzip \
     \
    --assembly GRCh38 \
    --species homo_sapiens \
    --cache \
    --cache_version 112 \
    --dir_cache ${PWD}/vep_cache \
    --fork 6

[nuno-agostinho]

Hi @poddarharsh15,

Hope you are having a great day!

Could you please confirm that your file dbNSFP4.8a_grch38.gz contains all the columns that you mentioned?

If not, please note that there are two dbNSFP 4.8 files with different data, as stated in the dbNSFP website:

Two branches of dbNSFP are provided: dbNSFP4.8a suitable for academic use, which includes all the resources, and dbNSFP4.8c suitable for commercial use, which does not include Polyphen2, VEST, REVEL, ClinPred, CADD, LINSIGHT, GenoCanyon.

Given that you mention you are missing some columns, including CADD, PolyPhen-2 and REVEL, maybe you are using the 4.8c file?

Looking forward to your reply!

Best regards, Nuno

[poddarharsh15]

Hi @nuno-agostinho Thank you so much answering.

I am using version 4.8a of dbNSFP, and I have read the README file, which confirms that all the required columns are present. However, when I run VEP, these columns do not appear in my VCF file. Additionally, I have followed the step how to extract and generate index file using tabix as mentioned on the VEP website.

[poddarharsh15]

Hi @nuno-agostinho Thank you so much answering.

I am using version 4.8a of dbNSFP, and I have read the README file, which confirms that all the required columns are present. However, when I run VEP, these columns do not appear in my VCF file. Additionally, I have followed the step how to extract and generate index file using tabix as mentioned on the VEP website. PS: if you need any vcf file as example for inspecting the results please let me know.

[poddarharsh15]

Hi @nuno-agostinho,

I've identified the issue: when using version 4.8a of dbNSFP, not all the columns are generated as expected. However, when I run the same process with version 4.7a, all the columns are present. I'm not sure why this is happening, but it seems specific to the newer version.

Best regards, HP

[nuno-agostinho]

Hi @poddarharsh15,

I cannot reproduce your issue: I downloaded dbNSFP 4.8a file and followed the instructions in the plugin documentation and it is working as expected.

Are you following the instructions in the plugin documentation? Could you please detail the commands that you run and what is not working?

Thanks, Nuno

[nuno-agostinho]

Hi @poddarharsh15,

I'll close this issue for now since we haven't heard back from you. If you still need help, feel free to reply here at any time.

Thanks, Nuno