Submissions for variant NM_022436.3(ABCG5):c.1550C>G (p.Thr517Ser)

gnomAD frequency: 0.01119  dbSNP: rs17031672

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000960558	SCV001107550	benign	Sitosterolemia	2024-01-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001143373	SCV001303894	benign	Sitosterolemia 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001574207	SCV001800982	likely benign	not provided	2021-08-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002400118	SCV002709427	benign	Cardiovascular phenotype	2020-11-16	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702538	SCV005204693	benign	not specified	2024-06-18	criteria provided, single submitter	clinical testing	Variant summary: ABCG5 c.1550C>G (p.Thr517Ser) results in a conservative amino acid change located in the ABC-2 type transporter, transmembrane domain (IPR013525) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0025 in 251418 control chromosomes, predominantly at a frequency of 0.036 within the African or African-American subpopulation in the gnomAD database, including 12 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 7.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCG5 causing Early Onset Coronary Artery Disease phenotype (0.005). To our knowledge, no occurrence of c.1550C>G 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: 779657). Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV001574207	SCV005263408	likely benign	not provided		criteria provided, single submitter	not provided