Submissions for variant NM_001378454.1(ALMS1):c.2661A>G (p.Val887=)

gnomAD frequency: 0.00818  dbSNP: rs76266696

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086073	SCV000290080	benign	Alstrom syndrome	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000441805	SCV000532097	benign	not specified	2016-10-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics	RCV000710531	SCV000840771	benign	not provided	2018-05-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000441805	SCV000864088	benign	not specified	2016-09-19	criteria provided, single submitter	clinical testing	Variant summary: The ALMS1 c.2658A>G (p.Val886Val, alternative name c.2664A>G) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict a creation of cryptic donor site. This silent variant is 100 nucleotides away from the exon-intron bounday; thus it is unlikely that the cryptic site will be used. In addition, these predictions have yet to be confirmed by functional studies. This variant was found in 310/120600 control chromosomes (3 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0278175 (272/9778). This frequency is about 12 times the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory has classified this variant as benign. Taken together, this variant is classified as a benign variant.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000441805	SCV000967039	benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Val886Val in exon 8 of ALMS1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 2.78% (272/9778) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs76266696).
Ambry Genetics	RCV002429129	SCV002743828	benign	Cardiovascular phenotype	2019-01-09	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001086073	SCV004564790	benign	Alstrom syndrome	2024-07-25	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000710531	SCV005242447	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001086073	SCV001458917	benign	Alstrom syndrome	2020-09-16	no assertion criteria provided	clinical testing