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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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Annotation Discrepancy for Variant 1:98348885_G>A in VEP 113 #1793

Open GSYongWu opened 4 days ago

GSYongWu commented 4 days ago

Hi, I observed that for the variant 1:98348885_G>A, the HGVSp annotation returned by VEP is p.C29=. However, the expected annotation should be p.R29C. This discrepancy might lead to confusion regarding the effect of this variant, as the amino acid change is significant. Could you please investigate this issue? It may help ensure the accuracy of the annotations provided by VEP for users relying on correct variant classifications. Thank you for your attention to this matter.

Best regards,

dglemos commented 4 days ago

Hi @GSYongWu, To further understand the issue, can you please send the full command you run to annotate the variant?

GSYongWu commented 4 days ago

Hi, My command is: "/usr/bin/perl ensembl-vep-release-113.0/vep --offline --no_stats --buffer_size 10000 --fork 4 --ccds --uniprot --hgvs --symbol --shift_3prime 1 --numbers --canonical --protein --biotype --hgvsg --variant_class --total_length --force_overwrite --allele_number --no_escape --vcf --dir vepdb --fasta genome/hs37d5.fa --format vcf --input_file clincal.merge.vcf --output_file clincal.merge.out.vep.vcf --refseq --use_given_ref --no_check_variants_order" I tested several hundred mutations and did not encounter this issue with the other mutations

GSYongWu commented 3 days ago

11:108183167_AT>GC has the same issue. the HGVSp annotation returned by VEP is p.S1983=. The expected annotation should be p.N1983S. Additionally, I found that the 10:89624327_C>T variant should be in the intron of PTEN, but the result is annotated upstream of KLLN.

dglemos commented 3 days ago

Thank you for sending more details. There is a bug in release 113 affecting refseq annotation, we are working on a fix that should go live very soon.

Additionally, I found that the 10:89624327_C>T variant should be in the intron of PTEN, but the result is annotated upstream of KLLN.

VEP returns intron_variant for gene PTEN, you check the result here: https://grch37.ensembl.org/Homo_sapiens/Tools/VEP/Ticket?tl=2AmWE5uJ9DQrGT9t