Submissions for variant NM_005502.4(ABCA1):c.3544G>A (p.Ala1182Thr)

gnomAD frequency: 0.00061  dbSNP: rs143180998

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000336016	SCV000476263	likely benign	Hypoalphalipoproteinemia, primary, 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.
Illumina Laboratory Services, Illumina	RCV000404479	SCV000476264	likely benign	Tangier disease	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779670	SCV000916390	likely benign	not specified	2018-05-29	criteria provided, single submitter	clinical testing	Variant summary: ABCA1 c.3544G>A (p.Ala1182Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00045 in 277128 control chromosomes (gnomAD and publications). The observed variant frequency is approximately 36 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCA1 causing Early Onset Coronary Artery Disease phenotype (1.3e-05), suggesting that the variant is benign. The variant, c.3544G>A, has not been reported in the literature in individuals affected with Early Onset Coronary Artery Disease and was reported in controls with normal HDL-C levels (Peloso_2016). However, this variant was also reported in one individual with low HDL-C (Dron_2017). 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV001093094	SCV001249915	uncertain significance	not provided	2019-12-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001093094	SCV002333187	likely benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004609371	SCV005110713	benign	Cardiovascular phenotype	2024-04-16	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.