ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.11824G>A (p.Gly3942Ser) (rs61741524)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000175336 SCV000226807 benign not specified 2014-08-27 criteria provided, single submitter clinical testing
GeneDx RCV000175336 SCV000533002 likely benign not specified 2017-11-16 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.
Invitae RCV000475832 SCV000554290 benign not provided 2019-02-27 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000175336 SCV000711945 benign not specified 2017-12-21 criteria provided, single submitter clinical testing p.Gly3940Ser in exon 18 of ALMS1: This variant is not expected to have clinical significance because it has been identified in 1.30% (309/24020) of African chro mosomes including 4 homozygotes by the Genome Aggregation Database (gnomAD, http ://; dbSNP rs61741524). ACMG/AMP criteria applied: BA1 .
Integrated Genetics/Laboratory Corporation of America RCV000175336 SCV000864123 benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.11818G>A (p.Gly3940Ser, alternative name c.11824G>A) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 277116 control chromosomes, predominantly within the African subpopulation at a frequency of 0.013 in the gnomAD database, including 4 homozygotes. The observed variant frequency within African control individuals is approximately 5.8 fold above 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 African origin. c.11818G>A has been reported in the literature in patients with clinical features of Alstrom syndrome. But this report does not provide unequivocal conclusions about association of the variant with cardiomyopathy or with Alstrom syndrome and is listed among a series of SNV's that were deemed as being unlikely to be pathogenic by the authors. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and 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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