[ensembl-dev] VEP missing annotation for intergenic-corrected variants

Luke Goodsell l.goodsell at achillestx.com
Tue Nov 21 14:32:19 GMT 2017


I have a couple of variants (listed below) that are missing output when run through vep v90.7 for GRCh37 RefSeq transcripts with the latest cache.


Example command:

    vep --input_file snvs.vcf --output_file snvs_annotated.vcf --dir_cache [PATH] --fasta [PATH] --cache --offline --assembly "GRCh37" --refseq --vcf

The output file is exactly the same as the input but with vep’s header lines added. I would expect at least something like “CSQ=C|intergenic_variant|MODIFIER||||||||||||||||||||||||||||” to be added to the INFO field to show that the variant was passed through vep.

I have reproduced this with the online VEP interface (http://grch37.ensembl.org/Homo_sapiens/Tools/VEP ; select “RefSeq transcripts” and set “Get regulatory region consequences” to “No”).

Comparing the positions in EnsEMBL’s genome browser and UCSC’s, these regions appear to be intergenic in EnsEMBL while in UCSC theyo hit RefSeq transcripts - a pseudogene (LOC645166) and a protein-coding gene (NBPF1) respectively. If I add the “--use_given_ref” flag, vep reports the same transcripts as UCSC. However, this raises two questions:

1. Is adding the “--use_given_ref” flag the right thing to do? Vep reports mismatches (“rseq_mrna_nonmatch&rseq_5p_mismatch&rseq_cds_mismatch&rseq_3p_mismatch&rseq_ens_no_match”), which suggests that this is not the best mapping for the transcript and hence why EnsEMBL’s alignment is different.

2. If I don’t add the “--use_given_ref” flag, why isn’t VEP reporting these variants as intergenic?

Kind regards,

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