[ensembl-dev] variant_effect_predictor.pl: --pick option selecting lower ranking consequence?

[Andrew Carson]

Hi Will,
I'm again seeing instances where running VEP with the --pick filtering option (variant_effect_predictor.pl script version 75) is picking lower consequence in some instances.
In this case, the most severe consequence is in a minor splice form, but I still want to "pick" this since it is the most severe consequence.
Here is an example in .vcf format:

5              170833402           .               C             T              .               PASS

The unfiltered/unpicked consequence is as follows (separated into the 7 different consequences):
T|ENSG00000181163|ENST00000519955|Transcript|downstream_gene_variant||||||COSM1065794|||||||||666|1|||NPM1|HGNC||||retained_intron||||||||||,
T|ENSG00000181163|ENST00000351986|Transcript|intron_variant||||||COSM1065794||||8/9||||||1|||NPM1|HGNC||||protein_coding|ENSP00000341168||CCDS4377.1|ENST00000351986.6:c.684+995C>T||||||,
T|ENSG00000181163|ENST00000517671|Transcript|intron_variant||||||COSM1065794||||10/11||||||1|||NPM1|HGNC||||protein_coding|ENSP00000428755||CCDS4376.1|ENST00000517671.1:c.771+995C>T||||||,
T|ENSG00000181163|ENST00000393820|Transcript|missense_variant&splice_region_variant|871|773|258|A/V|gCg/gTg|COSM1065794|||10/10|||||||1|||NPM1|HGNC|deleterious(0.01)|benign(0.002)||protein_coding|ENSP00000377408||CCDS43399.1|ENST00000393820.2:c.773C>T|ENSP00000377408.2:p.Ala258Val|||||,
T|ENSG00000181163|ENST00000524204|Transcript|upstream_gene_variant||||||COSM1065794|||||||||1095|1|||NPM1|HGNC||||retained_intron||||||||||,
T|ENSG00000181163|ENST00000296930|Transcript|intron_variant||||||COSM1065794||||9/10||||||1||YES|NPM1|HGNC||||protein_coding|ENSP00000296930||CCDS4376.1|ENST00000296930.5:c.771+995C>T||||||,
T||ENSR00001296571|RegulatoryFeature|regulatory_region_variant||||||COSM1065794||||||||||||||||||||||||||||

However, when I use the --pick option, I get the following consequence:
T|ENSG00000181163|ENST00000296930|Transcript|intron_variant||||||COSM1065794||||9/10||||||1||YES|NPM1|HGNC||||protein_coding|ENSP00000296930||CCDS4376.1|ENST00000296930.5:c.771+995C>T||||||
(Note, here is the command I use:
perl variant_effect_predictor.pl --everything --no_stats --cache -i file.vcf -o out.vcf --format vcf --dir /variant_effect_predictor/ --vcf --no_progress --pubmed --gmaf --maf_1kg --check_existing --check_alleles --pick

The most damaging consequence, however, is the missense_variant (the 4th consequence in the unfiltered/unpicked consequence.

Note, when I run this same variant through the VEP Web interface, I get the same consequence when selecting "Show one selected consequence per variant".

Is there a reason I'm getting the intron_variant using --pick instead of the missense_variant?
Any help would be greatly appreciated!

Andrew R. Carson, Ph.D.
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://mail.ensembl.org/pipermail/dev_ensembl.org/attachments/20140801/18643d80/attachment.html>