Submissions for variant NM_022437.3(ABCG8):c.491G>A (p.Arg164Gln)

gnomAD frequency: 0.00232  dbSNP: rs74358901

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000395777	SCV000342574	benign	not specified	2016-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001139254	SCV001299380	likely benign	Sitosterolemia 1	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001514945	SCV001722915	benign	not provided	2024-01-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002348017	SCV002646390	likely benign	Cardiovascular phenotype	2020-03-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV002494877	SCV002795536	likely benign	Gallbladder disease 4; Sitosterolemia 1	2021-11-02	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001139254	SCV003822414	likely benign	Sitosterolemia 1	2023-03-30	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001514945	SCV005256331	likely benign	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000395777	SCV005380882	likely benign	not specified	2024-08-08	criteria provided, single submitter	clinical testing	Variant summary: ABCG8 c.491G>A (p.Arg164Gln) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00062 in 250752 control chromosomes, predominantly at a frequency of 0.0085 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG8 causing Early Onset Coronary Artery Disease phenotype (0.005). To our knowledge, no occurrence of c.491G>A in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 288464). Based on the evidence outlined above, the variant was classified as likely benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV001514945	SCV005411688	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	BS1, PM1_supporting
PreventionGenetics, part of Exact Sciences	RCV003930153	SCV004750746	benign	ABCG8-related disorder	2019-06-05	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).