avinput changes InterVar annotation

[weizhu365]

Dear InterVar developers;

I have a variant chr7:124824014:TTA:T, and I presented it in two ways in the avinput:

1. chr7 124824015 124824016 TA - . 20625 .
2. chr7 124824014 124824016 TTA T

The format 1) is recommended by AnnoVar.

And the InterVar annotation results are different:

module load annovar

### Test "chr7    124824015       124824016       TA      -       .       20625   ."
cat test1.avinput
chr7    124824015       124824016       TA      -       .       20625   .

/home/zhuw10/git/InterVar-2.2.1/Intervar.py -i test1.avinput -b hg38 -d $ANNOVAR_DATA/hg38 -o test1 -t /home/zhuw10/git/InterVar-2.2.1/intervardb --table_annovar=$ANNOVAR_HOME/table_annovar.pl --convert2annovar=$ANNOVAR_HOME/convert2annovar.pl --annotate_variation=$ANNOVAR_HOME/annotate_variation.pl


 cat test1.hg38_multianno.txt.intervar
#Chr    Start   End     Ref     Alt     Ref.Gene        Func.refGene    ExonicFunc.refGene      Gene.ensGene    avsnp147        AAChange.ensGene        AAChange.refGene        clinvar: Clinvar         InterVar: InterVar and Evidence         Freq_gnomAD_genome_ALL  Freq_esp6500siv2_all    Freq_1000g2015aug_all   CADD_raw        CADD_phred      SIFT_score      GERP++_RS       phyloP46way_placental   dbscSNV_ADA_SCORE        dbscSNV_RF_SCORE        Interpro_domain AAChange.knownGene      rmsk    MetaSVM_score   Freq_gnomAD_genome_POPs OMIM    Phenotype_MIM   OrphaNumber     Orpha
7       124824015       124824016       TA      -       POT1    exonic  frameshift deletion     POT1    rs758673417     POT1:ENST00000654766.1:exon17:c.1626_1627del:p.D542Efs*9        POT1:NM_001042594:exon18:c.1458_1459del:p.D486Efs*9      clinvar: Conflicting_interpretations_of_pathogenicity    InterVar: Uncertain significance PVS1=1 PS=[0, 0, 0, 0, 0] PM=[0, 0, 0, 0, 0, 0, 0] PP=[0, 0, 0, 0, 0, 0] BA1=0 BS=[0, 0, 0, 0, 0] BP=[0, 0, 0, 0, 0, 0, 0, 0]  .       8e-05   .       .       .       .       .       .       .       .       .       POT1:ENST00000654766.1:exon17:c.1626_1627del:p.D542Efs*9..       AFR:.,AMR:.,EAS:.,FIN:.,NFE:.,OTH:.,ASJ:.       606478  615848;616568;  251627;251630;618;      251627|Oligodendroglioma|-|Not applicable|All ages|137800 616568~251630|Anaplastic oligodendroglioma|-|Not applicable|Adult|137800 616568~618|Familial melanoma|Unknown|Autosomal dominant<br>or&nbsp;Multigenic/multifactorial|Adult|155600 155601 155700 608035 609048 613099 613972 615134 615848~

### Test "chr7    124824014       124824016       TTA     T"
cat test2.avinput
chr7    124824014       124824016       TTA     T

/home/zhuw10/git/InterVar-2.2.1/Intervar.py -i test2.avinput -b hg38 -d $ANNOVAR_DATA/hg38 -o test2 -t /home/zhuw10/git/InterVar-2.2.1/intervardb --table_annovar=$ANNOVAR_HOME/table_annovar.pl --convert2annovar=$ANNOVAR_HOME/convert2annovar.pl --annotate_variation=$ANNOVAR_HOME/annotate_variation.pl

cat test2.hg38_multianno.txt.intervar
#Chr    Start   End     Ref     Alt     Ref.Gene        Func.refGene    ExonicFunc.refGene      Gene.ensGene    avsnp147        AAChange.ensGene        AAChange.refGene        clinvar: Clinvar         InterVar: InterVar and Evidence         Freq_gnomAD_genome_ALL  Freq_esp6500siv2_all    Freq_1000g2015aug_all   CADD_raw        CADD_phred      SIFT_score      GERP++_RS       phyloP46way_placental   dbscSNV_ADA_SCORE        dbscSNV_RF_SCORE        Interpro_domain AAChange.knownGene      rmsk    MetaSVM_score   Freq_gnomAD_genome_POPs OMIM    Phenotype_MIM   OrphaNumber     Orpha
7       124824014       124824016       TTA     T       POT1    exonic  frameshift substitution POT1    rs758673417     POT1:ENST00000654766.1:exon17:c.1626_1628delinsA:p.D542Efs*9    POT1:NM_001042594:exon18:c.1458_1460delinsA:p.D486Efs*9  clinvar: UNK     InterVar: Likely pathogenic PVS1=1 PS=[0, 0, 0, 0, 0] PM=[0, 1, 0, 0, 0, 0, 0] PP=[0, 0, 0, 0, 0, 0] BA1=0 BS=[0, 0, 0, 0, 0] BP=[0, 0, 0, 0, 0, 0, 0, 0]       .       .       .       .       .       .       .       .       .       .       .       POT1:ENST00000654766.1:exon17:c.1626_1628delinsA:p.D542Efs*9    .       .       AFR:.,AMR:.,EAS:.,FIN:.,NFE:.,OTH:.,ASJ:.        606478  615848;616568;  251627;251630;618;      251627|Oligodendroglioma|-|Not applicable|All ages|137800 616568~251630|Anaplastic oligodendroglioma|-|Not applicable|Adult|137800 616568~618|Familial melanoma|Unknown|Autosomal dominant<br>or&nbsp;Multigenic/multifactorial|Adult|155600 155601 155700 608035 609048 613099 613972 615134 615848~

I would like to know whether my avinput format 2) is wrong or there is a bug in InterVar.

Thanks,

Wei Zhu