Submissions for variant NM_003742.4(ABCB11):c.3556G>A (p.Glu1186Lys)

gnomAD frequency: 0.00943  dbSNP: rs1521808

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176656	SCV000228347	other	not provided	2018-05-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000254105	SCV000309815	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000254105	SCV000517791	benign	not specified	2016-07-12	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	RCV000176656	SCV001109056	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001133697	SCV001293407	benign	Progressive familial intrahepatic cholestasis type 2	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000254105	SCV002103712	benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: ABCB11 c.3556G>A (p.Glu1186Lys) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0021 in 249196 control chromosomes, predominantly at a frequency of 0.031 within the African or African-American subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 13.86 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCB11 causing Familial Intrahepatic Cholestasis phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000176656	SCV004183792	benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	ABCB11: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000176656	SCV005244715	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001133697	SCV001458318	benign	Progressive familial intrahepatic cholestasis type 2	2020-06-06	no assertion criteria provided	clinical testing