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</o:shapelayout></xml><![endif]--></head><body lang=EN-US link=blue vlink=purple><div class=WordSection1><p class=MsoNormal>Hi Will,<o:p></o:p></p><p class=MsoNormal>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.<o:p></o:p></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.<o:p></o:p></p><p class=MsoNormal>Here is an example in .vcf format:<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>5 170833402 . C T . PASS<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>The unfiltered/unpicked consequence is as follows (separated into the 7 different consequences):<o:p></o:p></p><p class=MsoNormal>T|ENSG00000181163|ENST00000519955|Transcript|downstream_gene_variant||||||COSM1065794|||||||||666|1|||NPM1|HGNC||||retained_intron||||||||||,<o:p></o:p></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||||||,<o:p></o:p></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||||||,<o:p></o:p></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|||||,<o:p></o:p></p><p class=MsoNormal>T|ENSG00000181163|ENST00000524204|Transcript|upstream_gene_variant||||||COSM1065794|||||||||1095|1|||NPM1|HGNC||||retained_intron||||||||||,<o:p></o:p></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||||||,<o:p></o:p></p><p class=MsoNormal>T||ENSR00001296571|RegulatoryFeature|regulatory_region_variant||||||COSM1065794||||||||||||||||||||||||||||<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>However, when I use the --pick option, I get the following consequence:<o:p></o:p></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||||||<o:p></o:p></p><p class=MsoNormal>(Note, here is the command I use:<o:p></o:p></p><p class=MsoNormal> 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<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>The most damaging consequence, however, is the missense_variant (the 4<sup>th</sup> consequence in the unfiltered/unpicked consequence.<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></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".<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal>Is there a reason I’m getting the intron_variant using --pick instead of the missense_variant?<o:p></o:p></p><p class=MsoNormal>Any help would be greatly appreciated!<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal><span style='font-family:"Myriad Pro","sans-serif"'>Andrew R. Carson, Ph.D.</span> <o:p></o:p></p></div></body></html>