Describe the bug
Currently the most severe consequence selection for MEI is a bit off. It can select non coding transcript consequences over coding sequence ones with the same effect, compare
17 29653204 . A <INS:ME> 17 . MEINFO=ALU,29653204,29653205,NA;NOT_VALIDATED;SVTYPE=INS;set=Intersection;FOUNDBY=1;ACC9292A2_lanes_1234_sorted_md_all_me_CHROM=.|17;ACC9292A2_lanes_1234_sorted_md_all_me_POS=.|29653204;ACC9292A2_lanes_1234_sorted_md_all_me_QUAL=.|17;ACC9292A2_lanes_1234_sorted_md_all_me_FILTERS=.|.;ACC9292A2_lanes_1234_sorted_md_all_me_SAMPLE=.|ACC9292A2|GT:1/1|GQ:17|FL:8|SP:18|CLIP5:1|CLIP3:1;ACC9292A2_lanes_1234_sorted_md_all_me_INFO=.|MEINFO:ALU:29653204:29653205:NA|NOT_VALIDATED|SVTYPE:INS;svdb_origin=ACC9292A2_lanes_1234_sorted_md_all_me;SUPP_VEC=1;CSQ=insertion|upstream_gene_variant|MODIFIER|EVI2A|ENSG00000126860|Transcript|ENST00000247270|protein_coding|||||||||||4438|-1||HGNC|3499|YES|||CCDS32608.1|ENSP00000247270|EVI2A_HUMAN||UPI000042B0AE|||Ensembl||||||||||||||,insertion|coding_sequence_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000356175|protein_coding|36/57||||5523|5140|1714|||||1||HGNC|7765||||CCDS11264.1|ENSP00000348498|NF1_HUMAN|Q9UMU3_HUMAN&Q4W6X4_HUMAN&K7EP94_HUMAN&H0UIC3_HUMAN|UPI000002AEF8|||Ensembl|||||||Gene3D:1.25.10.10&PROSITE_profiles:PS50191&PANTHER:PTHR10194&PANTHER:PTHR10194:SF60&SMART:SM00516|||||||,insertion|coding_sequence_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000358273|protein_coding|37/58||||5586|5203|1735|||||1||HGNC|7765|YES|||CCDS42292.1|ENSP00000351015|NF1_HUMAN|Q9UMU3_HUMAN&Q4W6X4_HUMAN&K7EP94_HUMAN|UPI000012FFAE|||Ensembl|||||||Gene3D:1.25.10.10&PROSITE_profiles:PS50191&PANTHER:PTHR10194&PANTHER:PTHR10194:SF60&SMART:SM00516|||||||,insertion|coding_sequence_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000456735|protein_coding|28/50||||4138|4138|1380|||||1|cds_start_NF|HGNC|7765|||||ENSP00000389907||Q4W6X4_HUMAN&H0Y465_HUMAN|UPI00016112B7|||Ensembl|||||||PROSITE_profiles:PS50191&PANTHER:PTHR10194&PANTHER:PTHR10194:SF60&SMART:SM00516|||||||,insertion|upstream_gene_variant|MODIFIER|EVI2A|ENSG00000126860|Transcript|ENST00000462804|protein_coding|||||||||||4303|-1||HGNC|3499||||CCDS42293.1|ENSP00000420557|EVI2A_HUMAN||UPI000042B0AD|||Ensembl||||||||||||||,insertion|upstream_gene_variant|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000479536|nonsense_mediated_decay|||||||||||4142|1|cds_start_NF|HGNC|7765|||||ENSP00000467080|||UPI0002840F85|||Ensembl||||||||||||||,insertion|non_coding_transcript_exon_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000493220|retained_intron|19/21||||3676|||||||1||HGNC|7765|||||||||||Ensembl||||||||||||||,insertion|3_prime_UTR_variant&NMD_transcript_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000579081|nonsense_mediated_decay|37/58||||5339|||||||1|cds_start_NF|HGNC|7765|||||ENSP00000462408||Q9UMU3_HUMAN&K7EP94_HUMAN&J3KSB5_HUMAN&H0UIC3_HUMAN|UPI000268B084|||Ensembl||||||||||||||,insertion|non_coding_transcript_exon_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000581113|processed_transcript|2/6||||520|||||||1||HGNC|7765|||||||||||Ensembl||||||||||||||,insertion|coding_sequence_variant&feature_elongation|MODIFIER|NF1|4763|Transcript|NM_000267.3|protein_coding|36/57||||5523|5140|1714|||||1||EntrezGene|7765|||||NP_000258.1||||||RefSeq||||OK||||||||||,insertion|upstream_gene_variant|MODIFIER|EVI2A|2123|Transcript|NM_001003927.3|protein_coding|||||||||||4565|-1||EntrezGene|3499|YES||||NP_001003927.1||||||RefSeq||||||||||||||,insertion|coding_sequence_variant&feature_elongation|MODIFIER|NF1|4763|Transcript|NM_001042492.3|protein_coding|37/58||||5536|5203|1735|||||1||EntrezGene|7765|YES||||NP_001035957.1||||||RefSeq||||||||||||||,insertion|upstream_gene_variant|MODIFIER|EVI2A|2123|Transcript|NM_014210.4|protein_coding|||||||||||4565|-1||EntrezGene|3499|||||NP_055025.2||||||RefSeq|||||||||||||| GT:GQ:FL:SP:CLIP5:CLIP3 1/1:17:8:18:1:1
and
17 29653204 . A <INS:ME> 17 . CSQ=insertion|non_coding_transcript_exon_variant&feature_elongation|MODIFIER|NF1|ENSG00000196712|Transcript|ENST00000581113|processed_transcript|2/6||||520|||||||1||HGNC|7765|||||||||||Ensembl||||||||||||||,insertion|upstream_gene_variant|MODIFIER|EVI2A|2123|Transcript|NM_014210.4|protein_coding|||||||||||4565|-1||EntrezGene|3499|||||NP_055025.2||||||RefSeq||||||||||||||;ACC9292A2_lanes_1234_sorted_md_all_me_CHROM=.|17;ACC9292A2_lanes_1234_sorted_md_all_me_FILTERS=.|.;ACC9292A2_lanes_1234_sorted_md_all_me_POS=.|29653204;SVTYPE=INS;ACC9292A2_lanes_1234_sorted_md_all_me_QUAL=.|17;FOUNDBY=1;MEINFO=ALU,29653204,29653205,NA;NOT_VALIDATED;SUPP_VEC=1;svdb_origin=ACC9292A2_lanes_1234_sorted_md_all_me;ACC9292A2_lanes_1234_sorted_md_all_me_SAMPLE=.|ACC9292A2|GT:1/1|GQ:17|FL:8|SP:18|CLIP5:1|CLIP3:1;ACC9292A2_lanes_1234_sorted_md_all_me_INFO=.|MEINFO:ALU:29653204:29653205:NA|NOT_VALIDATED|SVTYPE:INS;set=Intersection;most_severe_pli=0.9;most_severe_consequence=7765:insertion|non_coding_transcript_exon_variant,3499:insertion|upstream_gene_variant GT:GQ:FL:SP:CLIP5:CLIP3 1/1:17:8:18:1:1
for case trustykit.
This causes the variant to fall outside the clinical filter in Scout, although it can be found with meticulous searching in a small gene panel.
Expected behavior
Annotation closer to SNVs might be one option: since the MEI from RetroSeq are just one point ins we could treat them as SNV indels, leaving all transcripts and using the SNV most severe consequence. But it is probably wise also to inspect the order for SVs to make sure this is confined to MEI. 😊
Software version (please complete the following information):
Describe the bug
Currently the most severe consequence selection for MEI is a bit off. It can select non coding transcript consequences over coding sequence ones with the same effect, compare
and
for case
trustykit.This causes the variant to fall outside the clinical filter in Scout, although it can be found with meticulous searching in a small gene panel.
Expected behavior
Annotation closer to SNVs might be one option: since the MEI from RetroSeq are just one point ins we could treat them as SNV indels, leaving all transcripts and using the SNV most severe consequence. But it is probably wise also to inspect the order for SVs to make sure this is confined to MEI. 😊
Software version (please complete the following information):