Entering edit mode
2.8 years ago
najoshi
▴
30
So I am trying to figure out why this particular complex variant was annotated with an effect of "start_lost" when I don't see any evidence of the start codon being changed. Here is the full vcf line:
chr1 20717668 . ACGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAA GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC 566.598 . AB=0.347826;ABP=12.2627;AC=5;AF=0.5;AN=10;AO=16;CIGAR=1X57M1X;DP=46;DPB=46.1525;DPRA=0;EPP=5.18177;EPPR=4.16842;GTI=0;LEN=59;MEANALT=1;MQM=60;MQMR=60;NS=5;NUMALT=1;ODDS=5.38955;PAIRED=0.5625;PAIREDR=0.466667;PAO=9;PQA=333;PQR=0;PRO=0;QA=586;QR=1103;RO=30;RPL=13;RPP=16.582;RPPR=31.9633;RPR=3;RUN=1;SAF=7;SAP=3.55317;SAR=9;SRF=8;SRP=17.1973;SRR=22;TYPE=complex;ANN=GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|start_lost|HIGH|KIF17|KIF17|transcript|NM_020816.4|protein_coding|1/15|c.-20_39delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|p.MetAlaSerGluAlaValLysValValValArgCysArg1?|340/3961|1/3090|1/1029||,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|start_lost|HIGH|KIF17|KIF17|transcript|NM_001122819.3|protein_coding|1/15|c.-20_39delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|p.MetAlaSerGluAlaValLysValValValArgCysArg1?|340/3958|1/3087|1/1028||,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|5_prime_UTR_variant|MODIFIER|KIF17|KIF17|transcript|NM_020816.4|protein_coding|1/15|c.-20_39delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC||||||,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|5_prime_UTR_variant|MODIFIER|KIF17|KIF17|transcript|NM_001122819.3|protein_coding|1/15|c.-20_39delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC||||||,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|5_prime_UTR_variant|MODIFIER|KIF17|KIF17|transcript|NM_001287212.2|protein_coding|1/15|c.-447_-389delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2098|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|downstream_gene_variant|MODIFIER|SH2D5|SH2D5|transcript|NM_001103161.2|protein_coding||c.*4066_*4124delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2063|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|downstream_gene_variant|MODIFIER|SH2D5|SH2D5|transcript|XM_011541459.2|protein_coding||c.*4066_*4124delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2063|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|downstream_gene_variant|MODIFIER|SH2D5|SH2D5|transcript|XM_011541460.2|protein_coding||c.*4066_*4124delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2063|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|downstream_gene_variant|MODIFIER|SH2D5|SH2D5|transcript|XM_011541462.2|protein_coding||c.*4066_*4124delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2063|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|downstream_gene_variant|MODIFIER|SH2D5|SH2D5|transcript|XM_011541461.2|protein_coding||c.*4066_*4124delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2063|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|downstream_gene_variant|MODIFIER|SH2D5|SH2D5|transcript|NM_001103160.2|protein_coding||c.*4066_*4124delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|||||2063|,GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|intron_variant|MODIFIER|LOC107985528|LOC107985528|transcript|unknown_transcript_1|protein_coding|987/1510|c.167449+904178_167449+904236delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC||||||WARNING_TRANSCRIPT_MULTIPLE_STOP_CODONS;LOF=(KIF17|KIF17|3|0.67) GT:DP:AD:RO:QR:AO:QA:GL 0/1:4:3,1:3:111:1:37:-2.49371,0,-9.14896 0/1:9:6,3:6:221:3:109:-13.5154,0,-16.9355 0/1:11:6,5:6:223:5:182:-16.4518,0,-16.8162 0/1:12:8,4:8:294:4:149:-22.2684,0,-21.995 0/1:10:7,3:7:254:3:109:-13.2144,0,-19.5986
The first annotation looks like this:
GCGGCAGCGCACGACAACCTTCACCGCCTCGGAGGCCATGGCGCCGCGCCCAGGACCAC|start_lost|HIGH|KIF17|KIF17|transcript|NM_020816.4|protein_coding|1/15|c.-20_39delTTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGTinsGTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC|p.MetAlaSerGluAlaValLysValValValArgCysArg1?|340/3961|1/3090|1/1029||
For some reason it is calling it a deletion & insertion instead of just two separate SNPs. Looking at the two sequences:
TTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGT
GTGGTCCTGGGCGCGGCGCCATGGCCTCCGAGGCGGTGAAGGTTGTCGTGCGCTGCCGC
you can see that all of the bases are the same except for the first and last bases. The start codon is in the middle, i.e. this variant crosses the 5'UTR to exon 1 boundary. However, the start codon does not change, so why is it being annotated as a "start_lost"?
