Submissions for variant NM_003742.4(ABCB11):c.851T>C (p.Val284Ala)

gnomAD frequency: 0.00025  dbSNP: rs200739891

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000730938	SCV000521289	likely benign	not provided	2019-02-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 16763017, 14999697, 23022423, 19101985, 17181454, 19571440, 22795478, 28733223)
Eurofins Ntd Llc (ga)	RCV000730938	SCV000858705	uncertain significance	not provided	2017-12-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001133958	SCV001293675	uncertain significance	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000730938	SCV002035004	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000730938	SCV002038267	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003392240	SCV004119539	uncertain significance	ABCB11-related disorder	2024-04-18	no assertion criteria provided	clinical testing	The ABCB11 c.851T>C variant is predicted to result in the amino acid substitution p.Val284Ala. This variant was reported in one patient with progressive familial intrahepatic cholestasis (reported using the gene name BSEP in Table S5, Dröge et al. 2017. PubMed ID: 28733223). Different substitutions affecting the same residue (p.Val284Asp and p.Val284Leu) were reported to be associated with progressive familial intrahepatic cholestasis or Intrahepatic cholestasis of pregnancy (Anzivino et al. 2013. PubMed ID: 23022423; Chen et al. 2008. PubMed ID: 18692205; Chen et al. 2008. PubMed ID: 18853996). Cell based studies suggest that the p.Val284Ala substitution lead to increased level of mature protein (Byrne et al. 2009. PubMed ID: 19101985). This variant is reported in 0.044% of alleles in individuals of European (Finnish) descent in gnomAD. Although we suspect this variant could be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.