Submissions for variant NM_005502.4(ABCA1):c.5774G>A (p.Arg1925Gln)

gnomAD frequency: 0.00227  dbSNP: rs142688906

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000361601	SCV000476206	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.
Illumina Laboratory Services, Illumina	RCV000398410	SCV000476207	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779673	SCV000916393	benign	not specified	2017-12-18	criteria provided, single submitter	clinical testing	Variant summary: The ABCA1 c.5774G>A (p.Arg1925Gln) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 26674/299392 control chromosomes (3 homozygotes), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.011096 (282/25414). This frequency is about 888 times the estimated maximal expected allele frequency of a pathogenic ABCA1 variant (0.0000125), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. This variant has been reported in individuals with both high and low level of HDL-C, all without strong evidence for causality (Mantring 2007, Peloso 2016). The variant was also reported in a patient with Scott syndrome where authors found in in vitro experiments a decreased expression and impaired trafficking of the variant protein to the plasma membrane; however the authors speculated that another mutation, which remains to be identified, might also play a role in this phenotype (Albrecht 2005). In addition, one clinical diagnostic laboratory classified this variant as likely benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001522662	SCV001732249	benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001522662	SCV001986257	uncertain significance	not provided	2024-01-02	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect on protein trafficking and expression (PMID: 15790791); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 17383594, 15790791, 25215231, 16855366, 16704350, 28870971)
Genetic Services Laboratory, University of Chicago	RCV000779673	SCV002066270	likely benign	not specified	2019-08-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002356492	SCV002652103	likely benign	Cardiovascular phenotype	2020-06-23	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.
CeGaT Center for Human Genetics Tuebingen	RCV001522662	SCV004010847	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ABCA1: BS2