From: Spectrum of genomic variations in Indian patients with progressive familial intrahepatic cholestasis
Gene showing sequence variation | Subject ID | History of consanguinity | Nature of variation | Nucleotide change | Type of mutation | AA change | In silico prediction | Inclusion in databasesa | Population frequency (in ExAC) |
---|---|---|---|---|---|---|---|---|---|
‘Pathogenic’/ likely pathogenic variations | |||||||||
ATP8B1 | PF05 | Yes | Homozygous | c.[589_592inv;592_593insA] GGAG ⇒ CTCCA | Frame-shift; truncation after 205 amino acids | p.Gly197LeufsTer10 | Deleterious | Novelb | |
PF20 | No | Homozygous | c.1587_1589delCTT CTT ⇒ - | In-frame deletion of one amino acid | p.Phe529del | Deleterious | rs756395915, 18:55351308 CAAG/C | 8.24 × 10− 6 | |
PF19 | Yes | Homozygous | c.1660G > A | Mis-sense (GAT⇒AAT) | p.Asp554Asn | rs121909101, CM004386 ClinVar:7269 | |||
PF18 | No | Homozygous | c.2941G > A | Mis-sense (GAG⇒AAG) | p.Glu981Lys | Deleterious | CM096608 | ||
ABCB11 | PF03 | Yes | Homozygous | c.548 T > C | Mis-sense (ATG ⇒ ACG) | p.Met183Thr | Deleterious | CM103530 | |
PF13 | Yes | Homozygous | c.1360delG | Truncation after 453 amino acids | p.Val454* | Deleterious | Novel | ||
ABCB4 | PF25 | Yes | Homozygous | c.431G > A | Mis-sense (CGA ⇒ CAA) | p.Arg144Gln | Likely deleterious | rs863225299, ClinVar:217883 | 3.3 × 10− 5 |
Variation of ‘uncertain significance’ | |||||||||
ABCB11 | PF21 | No | Heterozygousc | c.784 + 1 G > C | Splice site variation | Possible abnormal splicing | Deleterious | Novel | |
ABCB4 | PF09 | No | Heterozygous | c.475C > T | Truncation after 474 amino acids (CGA ⇒ TGA) | p.Arg159* | Deleterious | rs377160065, CM075939, 7:87082321 G/A | 3.2 × 10− 5 |