ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.1270G>A (p.Val424Ile) (rs45630557)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234139 SCV000290072 benign Alstrom syndrome 2018-01-05 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000435494 SCV000510969 likely benign not provided 2016-09-12 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
GeneDx RCV000434450 SCV000528959 likely benign not specified 2018-01-02 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.
Genetic Services Laboratory, University of Chicago RCV000434450 SCV000593109 likely benign not specified 2016-12-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000434450 SCV000864106 benign not specified 2018-05-21 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.1267G>A (p.Val423Ile, alternative name c.1270G>A) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0028 in 276990 control chromosomes, predominantly found within the South Asian subpopulation with a frequency of 0.0051 in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2.3 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. At least one publication reports experimental evidence, demonstrating no sign of exon skipping with normal ALMS1 expression and without discernible defects in ciliary morphology in a cell line established from an individual carrying the variant (Chen 2017). These results indicate no damaging effect for this variant. Four 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000434450 SCV000967143 likely benign not specified 2016-03-21 criteria provided, single submitter clinical testing p.Val423Ile in exon 6 of ALMS1: This variant is not expected to have clinical si gnificance because it has been identified in 0.50% (82/16512) of South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs45630557).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.