Submissions for variant NM_001378454.1(ALMS1):c.11872+18G>A

gnomAD frequency: 0.00482  dbSNP: rs139647347

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000424257	SCV000529353	benign	not specified	2016-10-11	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514668	SCV000610541	likely benign	not provided	2017-03-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000424257	SCV001338983	benign	not specified	2020-03-30	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.11869+18G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0052 in 245654 control chromosomes in the gnomAD database, including 8 homozygotes. The observed variant frequency is approximately 2.34 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.11869+18G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521079	SCV001730337	benign	Alstrom syndrome	2025-02-03	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV001521079	SCV002538653	uncertain significance	Alstrom syndrome		criteria provided, single submitter	research	Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no literature is found to ascertain the role of rs139647347 in Alstrom syndrome yet.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001521079	SCV005879484	benign	Alstrom syndrome	2024-08-21	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000424257	SCV001920322	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000424257	SCV001959622	benign	not specified		no assertion criteria provided	clinical testing