<div dir="ltr">Hi Andrew,<div><br></div><div>The reason you are seeing this is because ENST00000296930 is the canonical transcript for that gene.</div><div><br></div><div>The sort order for --pick is:</div><div><br></div><div>
1) canonical status</div><div>2) biotype (priority given to protein coding)</div><div>3) consequence rank</div><div>4) transcript length</div><div><br></div><div>The reason --pick exists is because a lot of people want the "the" consequence for "the" transcript; the canonical status is Ensembl's way of saying this might be "the" transcript.</div>
<div><br></div><div>However, I can certainly understand other users that want to prioritise consequence rank above this, but then if we chose this method we may have other users complaining that --pick had chosen a missense variant in a transcript which is biologically irrelevant or even not real.</div>
<div><br></div><div>The solution is to allow users to customise this sort order, and it's something we'll be working on including in the future, probably via a plugin module.</div><div><br></div><div>For release 76 there is a --flag_pick option that just flags the picked consequence instead of removing all of the others, to allow you to assess what Ensembl thinks is the pick vs what you might choose.</div>
<div><br></div><div>You could also edit the code yourself; it would be a case of just moving some lines around, the code is in ensembl-variation/modules/Bio/EnsEMBL/Variation/Utils/VEP.pm, around line 1886.</div><div><br>
</div><div>Hope that helps</div><div><br></div><div>Will McLaren</div><div>Ensembl Variation</div><div><br></div><div><br></div><div><br></div></div><div class="gmail_extra"><br><br><div class="gmail_quote">On 1 August 2014 18:33, Andrew Carson <span dir="ltr"><<a href="mailto:acarson@invivoscribe.com" target="_blank">acarson@invivoscribe.com</a>></span> wrote:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex"><div lang="EN-US" link="blue" vlink="purple"><div><p class="MsoNormal">Hi Will,<u></u><u></u></p><p class="MsoNormal">I’m again seeing instances where running VEP with the --pick filtering option (<a href="http://variant_effect_predictor.pl" target="_blank">variant_effect_predictor.pl</a> script version 75) is picking lower consequence in some instances.<u></u><u></u></p>
<p class="MsoNormal">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.<u></u><u></u></p><p class="MsoNormal">Here is an example in .vcf format:<u></u><u></u></p>
<p class="MsoNormal"><u></u> <u></u></p><p class="MsoNormal">5 170833402 . C T . PASS<u></u><u></u></p><p class="MsoNormal"><u></u> <u></u></p><p class="MsoNormal">
The unfiltered/unpicked consequence is as follows (separated into the 7 different consequences):<u></u><u></u></p><p class="MsoNormal">T|ENSG00000181163|ENST00000519955|Transcript|downstream_gene_variant||||||COSM1065794|||||||||666|1|||NPM1|HGNC||||retained_intron||||||||||,<u></u><u></u></p>
<p class="MsoNormal">T|ENSG00000181163|ENST00000351986|Transcript|intron_variant||||||COSM1065794||||8/9||||||1|||NPM1|HGNC||||protein_coding|ENSP00000341168||CCDS4377.1|ENST00000351986.6:c.684+995C>T||||||,<u></u><u></u></p>
<p class="MsoNormal">T|ENSG00000181163|ENST00000517671|Transcript|intron_variant||||||COSM1065794||||10/11||||||1|||NPM1|HGNC||||protein_coding|ENSP00000428755||CCDS4376.1|ENST00000517671.1:c.771+995C>T||||||,<u></u><u></u></p>
<p class="MsoNormal">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|||||,<u></u><u></u></p>
<p class="MsoNormal">T|ENSG00000181163|ENST00000524204|Transcript|upstream_gene_variant||||||COSM1065794|||||||||1095|1|||NPM1|HGNC||||retained_intron||||||||||,<u></u><u></u></p><p class="MsoNormal">T|ENSG00000181163|ENST00000296930|Transcript|intron_variant||||||COSM1065794||||9/10||||||1||YES|NPM1|HGNC||||protein_coding|ENSP00000296930||CCDS4376.1|ENST00000296930.5:c.771+995C>T||||||,<u></u><u></u></p>
<p class="MsoNormal">T||ENSR00001296571|RegulatoryFeature|regulatory_region_variant||||||COSM1065794||||||||||||||||||||||||||||<u></u><u></u></p><p class="MsoNormal"><u></u> <u></u></p><p class="MsoNormal">However, when I use the --pick option, I get the following consequence:<u></u><u></u></p>
<p class="MsoNormal">T|ENSG00000181163|ENST00000296930|Transcript|intron_variant||||||COSM1065794||||9/10||||||1||YES|NPM1|HGNC||||protein_coding|ENSP00000296930||CCDS4376.1|ENST00000296930.5:c.771+995C>T||||||<u></u><u></u></p>
<p class="MsoNormal">(Note, here is the command I use:<u></u><u></u></p><p class="MsoNormal"> perl <a href="http://variant_effect_predictor.pl" target="_blank">variant_effect_predictor.pl</a> --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<u></u><u></u></p>
<p class="MsoNormal"><u></u> <u></u></p><p class="MsoNormal">The most damaging consequence, however, is the missense_variant (the 4<sup>th</sup> consequence in the unfiltered/unpicked consequence.<u></u><u></u></p><p class="MsoNormal">
<u></u> <u></u></p><p class="MsoNormal">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".<u></u><u></u></p><p class="MsoNormal">
<u></u> <u></u></p><p class="MsoNormal">Is there a reason I’m getting the intron_variant using --pick instead of the missense_variant?<u></u><u></u></p><p class="MsoNormal">Any help would be greatly appreciated!<u></u><u></u></p>
<p class="MsoNormal"><u></u> <u></u></p><p class="MsoNormal"><span style="font-family:"Myriad Pro","sans-serif"">Andrew R. Carson, Ph.D.</span> <u></u><u></u></p></div></div><br>_______________________________________________<br>
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<br></blockquote></div><br></div>