Submissions for variant NM_001374385.1(ATP8B1):c.1177A>G (p.Ile393Val)

gnomAD frequency: 0.00388  dbSNP: rs34315917

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000246161	SCV000311147	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000246161	SCV000342199	likely benign	not specified	2016-05-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000344311	SCV000409734	likely benign	Progressive familial intrahepatic cholestasis type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000246161	SCV000522427	benign	not specified	2016-02-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000971960	SCV001119643	benign	not provided	2025-01-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000971960	SCV001746549	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ATP8B1: BS1
Mayo Clinic Laboratories, Mayo Clinic	RCV000971960	SCV002541468	uncertain significance	not provided	2022-11-28	criteria provided, single submitter	clinical testing	BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000246161	SCV002548379	benign	not specified	2022-05-10	criteria provided, single submitter	clinical testing	Variant summary: ATP8B1 c.1177A>G (p.Ile393Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.004 in 251424 control chromosomes (gnomAD), predominantly at a frequency of 0.0061 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATP8B1 causing Familial Intrahepatic Cholestasis phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters have assessed the variant since 2014: three classified the variant as likely benign and two as benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000971960	SCV005207919	likely benign	not provided		criteria provided, single submitter	not provided