Submissions for variant NM_005502.4(ABCA1):c.3542C>T (p.Ser1181Phe)

gnomAD frequency: 0.00145  dbSNP: rs76881554

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000282087	SCV000476265	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	RCV000337098	SCV000476266	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.
Baylor Genetics	RCV000282087	SCV001530319	uncertain significance	Hypoalphalipoproteinemia, primary, 1	2018-10-25	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. This variant have been previously reported in individuals with high density lipoprotein (HDL) deficiency or abnormal cholesterol levels [PMID 15297675, 20981092, 20880529, 26255038, 24497850]
Invitae	RCV001490048	SCV001694604	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001526897	SCV001737643	benign	not specified	2021-05-24	criteria provided, single submitter	clinical testing	Variant summary: ABCA1 c.3542C>T (p.Ser1181Phe) results in a non-conservative amino acid change located in the ABC transporter-like domain (IPR003439) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0013 in 251430 control chromosomes, predominantly at a frequency of 0.002 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 160- fold the estimated maximal expected allele frequency for a pathogenic variant in ABCA1 causing Early Onset Coronary Artery Disease phenotype (1.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.3542C>T has been reported in the literature in individuals affected with low HDL cholesterol (e.g. Cohen_2004, Candini_2010, Tietjen_2012). However, the variant has also been found at a similar frequency in cases and controls in a study of individuals with early onset myocaridal infarction (e.g. Beaudoin_2012). These reports 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 cited the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics	RCV002338955	SCV002619183	likely benign	Cardiovascular phenotype	2019-10-21	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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001490048	SCV004225068	uncertain significance	not provided	2022-10-03	criteria provided, single submitter	clinical testing	BS1