ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.12362+18A>T

gnomAD frequency: 0.00525  dbSNP: rs535484933
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667907 SCV000792431 likely benign Alstrom syndrome 2017-06-22 criteria provided, single submitter clinical testing
GeneDx RCV000839162 SCV000981046 likely benign not provided 2018-06-14 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001260368 SCV001437316 benign not specified 2020-09-24 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.12359+18A>T (aka c.12365+18A>T) alters 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 0.0011 in 250814 control chromosomes, predominantly at a frequency of 0.015 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 8 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Alstrom Syndrome with Dilated Cardiomyopathy phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.12359+18A>T in individuals affected with Alstrom Syndrome with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000667907 SCV001727258 benign Alstrom syndrome 2024-01-29 criteria provided, single submitter clinical testing

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