Submissions for variant NM_001378454.1(ALMS1):c.12115-8del

dbSNP: rs748193431

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175433	SCV001338984	benign	not specified	2020-03-23	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.12112-8delT involves the deletion of a non-conserved 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 0.0075 in 142384 control chromosomes (gnomAD). The observed variant frequency within control individuals in the gnomAD database is approximately 3.3-fold the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism. The variant has been reported in at least one individual with Alstrom Syndrome in the literature, however this individual was also homozygous for another reportedly pathogenic variant (ALMS1 c.9749C>A, p.Ser3250X), providing supporting evidence for a benign role (e.g. Tasdemir_2013, Ozanturk_2015). One ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV001520129	SCV001729157	benign	Alstrom syndrome	2024-01-28	criteria provided, single submitter	clinical testing