Submissions for variant NM_022436.3(ABCG5):c.1567A>G (p.Ile523Val)

gnomAD frequency: 0.00189  dbSNP: rs140899003

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000595235	SCV000709628	likely benign	not specified	2017-06-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001143372	SCV001303893	uncertain significance	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). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521409	SCV001730749	benign	Sitosterolemia	2025-02-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001584407	SCV001812304	likely benign	not provided	2020-07-30	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24503134)
Genetic Services Laboratory, University of Chicago	RCV000595235	SCV002070903	likely benign	not specified	2021-06-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002404614	SCV002707232	benign	Cardiovascular phenotype	2019-07-12	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
CeGaT Center for Human Genetics Tuebingen	RCV001584407	SCV004146001	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	ABCG5: BP4, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000595235	SCV005185385	uncertain significance	not specified	2024-05-07	criteria provided, single submitter	clinical testing	Variant summary: ABCG5 c.1567A>G (p.Ile523Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 1614184 control chromosomes in the gnomAD database, including 10 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCG5 causing Early Onset Coronary Artery Disease (0.0019 vs 0.005), allowing no conclusion about variant significance. c.1567A>G has been reported in the literaturein at-least one patient suspected of partial lipodystrophy without strong evidence for causality (example: Johansen_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Early Onset Coronary Artery Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 24503134, 32088153). ClinVar contains an entry for this variant (Variation ID: 502765). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001584407	SCV001931328	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000595235	SCV001978780	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915740	SCV004729677	likely benign	ABCG5-related disorder	2019-05-07	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).