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<p class="MsoNormal"><span style="font-size:11.0pt;font-family:Calibri;mso-fareast-language:EN-US">Hello Will,<br>
<br>
Thank you very much, I think that clears it up. It looks like the variant position lies in BAP1-014 and not BAP1-201 but that still isn’t the primary transcript so it was not reported using per_gene.<br>
<br>
Thanks again.<br>
<br>
Regards,<br>
Aravind<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt;font-family:Calibri;mso-fareast-language:EN-US"><o:p> </o:p></span></p>
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<p class="MsoNormal"><b><span style="font-family:Calibri;color:black">From: </span>
</b><span style="font-family:Calibri;color:black"><dev-bounces@ensembl.org> on behalf of Will McLaren <wm2@ebi.ac.uk><br>
<b>Reply-To: </b>Ensembl developers list <dev@ensembl.org><br>
<b>Date: </b>Thursday, 20 October 2016 at 13:45<br>
<b>To: </b>Ensembl developers list <dev@ensembl.org><br>
<b>Subject: </b>Re: [ensembl-dev] Choosing the --per_gene option in VEP<o:p></o:p></span></p>
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<p class="MsoNormal">Hi Aravind, <o:p></o:p></p>
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<p class="MsoNormal"><o:p> </o:p></p>
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<p class="MsoNormal">The output selected is not by default based primarily on the consequence ranking, but on the likely relevance of each affected transcript.<o:p></o:p></p>
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<p class="MsoNormal"><o:p> </o:p></p>
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<p class="MsoNormal">The default order of selection criteria is shown in the documentation [1], and you may change this order with --pick_order if you wish to, for example, prioritise consequence rank first.<o:p></o:p></p>
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<p class="MsoNormal"><o:p> </o:p></p>
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<p class="MsoNormal">Without having seen your input, it seems likely that your variant of interest falls in an exon not found in the primary transcript of BAP1; if you study the transcript diagrams [2] you can see several transcripts contain exons (e.g. BAP1-201)
that are not found in the primary transcript as determined by CCDS, APPRIS and TSL (BAP1-001). This means it may have a missense effect in BAP1-201 but fall in the intron of BAP1-001.<o:p></o:p></p>
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<p class="MsoNormal"><o:p> </o:p></p>
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<p class="MsoNormal">Hope that helps<o:p></o:p></p>
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<p class="MsoNormal"><br>
Will McLaren<o:p></o:p></p>
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<p class="MsoNormal">Ensembl Variation<o:p></o:p></p>
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<p class="MsoNormal"><o:p> </o:p></p>
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<p class="MsoNormal">[1] : <a href="http://www.ensembl.org/info/docs/tools/vep/script/vep_other.html#pick">http://www.ensembl.org/info/docs/tools/vep/script/vep_other.html#pick</a><o:p></o:p></p>
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<p class="MsoNormal">[2] : <a href="http://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000163930;r=3:52401013-52410350">
http://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000163930;r=3:52401013-52410350</a><o:p></o:p></p>
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<p class="MsoNormal"><o:p> </o:p></p>
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<p class="MsoNormal">On 20 October 2016 at 13:35, Aravind Sankar <<a href="mailto:as42@sanger.ac.uk" target="_blank">as42@sanger.ac.uk</a>> wrote:<o:p></o:p></p>
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<p class="MsoNormal" style="mso-margin-top-alt:auto;mso-margin-bottom-alt:auto"><span style="font-size:11.0pt">Hello,<br>
<br>
I have been using the --per_gene option in VEP to get only the most severe consequence of each gene in the CSQ field for my files (as given in the documentation here
<a href="http://www.ensembl.org/info/docs/tools/vep/script/vep_options.html#opt_per_gene" target="_blank">
http://www.ensembl.org/info/docs/tools/vep/script/vep_options.html#opt_per_gene</a>). However, I noticed something going awry today. I was checking all the consequences of a particular position in a gene (BAP1). When I give the --per_gene option in vep, it
returns a single consequence for the variant and the consequence is an intron variant. When I don’t give the –per_gene option, it returns all the possible consequences for BAP1, which includes both a missense variant and an intron variant. For some reason,
the missense variant is not being reported over the intron variant while using the –per_gene option. I ran this on build 84. The commands I used were as follows:-<br>
<br>
Using per_gene :<br>
<br>
perl /software/vertres/bin-external/<a href="http://variant_effect_predictor_v84.pl" target="_blank">variant_effect_predictor_v84.pl</a> --offline --vcf --dir_cache /lustre/scratch116/vr/ref/ensembl/vep_cache --species homo_sapiens --assembly GRCh38 --no_progress
--everything --cache --per_gene -i bap1_pos_test.vcf -o bap1_84_per_gene.vcf</span><o:p></o:p></p>
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Without per_gene : <br>
<br>
perl /software/vertres/bin-external/<a href="http://variant_effect_predictor_v84.pl" target="_blank">variant_effect_predictor_v84.pl</a> --offline --vcf --dir_cache /lustre/scratch116/vr/ref/ensembl/vep_cache --species homo_sapiens --assembly GRCh38 --no_progress
--everything --cache -i bap1_pos_test.vcf -o bap1_84.vcf<br>
<br>
The output of the per_gene file doesn’t have the missense variant while the normal one does, for the same gene.
</span><span style="font-size:11.0pt;font-family:MingLiU"><br>
</span><span style="font-size:11.0pt">less bap1_84_per_gene.vcf | grep -c "missense"</span><o:p></o:p></p>
<p class="MsoNormal" style="mso-margin-top-alt:auto;mso-margin-bottom-alt:auto"><span style="font-size:11.0pt">0</span><o:p></o:p></p>
<p class="MsoNormal" style="mso-margin-top-alt:auto;mso-margin-bottom-alt:auto"><span style="font-size:11.0pt"><br>
less bap1_84.vcf | grep -c "missense"</span><o:p></o:p></p>
<p class="MsoNormal" style="mso-margin-top-alt:auto;mso-margin-bottom-alt:auto"><span style="font-size:11.0pt">1</span><o:p></o:p></p>
<p class="MsoNormal" style="mso-margin-top-alt:auto;margin-bottom:12.0pt"><span style="font-size:11.0pt"><br>
This is contrary to what is expected from the given documentation. Could someone help clarify what is going on here ?<br>
<br>
Thanking you,<br>
Aravind<br>
<br>
<br>
</span><o:p></o:p></p>
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