ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.12115-8del (rs748193431)

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Total submissions: 2
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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 2020-11-14 criteria provided, single submitter clinical testing

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