ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.5245A>G (p.Thr1749Ala)

gnomAD frequency: 0.00001  dbSNP: rs546111188
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000192985 SCV000246359 likely benign not specified 2015-05-27 criteria provided, single submitter clinical testing
Invitae RCV000867580 SCV001008824 benign Alstrom syndrome 2021-12-15 criteria provided, single submitter clinical testing
GeneDx RCV001640283 SCV001860159 benign not provided 2019-07-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26352687)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000192985 SCV002103894 benign not specified 2022-02-18 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.5242A>G/p.Thr1748Ala (also known as c.5248A>G in RefSeq) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0019 in 249000 control chromosomes, predominantly at a frequency of 0.015 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 6.71 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 a benign polymorphism found primarily in populations of South Asian origin. Three 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.

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