ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.12362+16_12362+17del (rs563514664)

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Total submissions: 3
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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 RCV001260367 SCV001437315 benign not specified 2020-09-24 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.12359+16_12359+17delCA (also referred to as c.12365+16_12365+17delCA) 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 250884 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 8.2 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+16_12359+17delCA in individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV001518548 SCV001727257 benign Alstrom syndrome 2020-11-25 criteria provided, single submitter clinical testing
GeneDx RCV001587299 SCV001825686 likely benign not provided 2019-09-19 criteria provided, single submitter clinical testing

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