ClinVar Miner

Submissions for variant NM_000091.4(COL4A3):c.4295G>A (p.Arg1432His) (rs200509072)

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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 RCV000597767 SCV000707547 uncertain significance not provided 2017-04-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764365 SCV000895399 uncertain significance Alport syndrome 3, autosomal dominant; Alport syndrome, autosomal recessive; Benign familial hematuria 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000597767 SCV001067203 likely benign not provided 2020-12-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174854 SCV001338244 likely benign not specified 2020-02-03 criteria provided, single submitter clinical testing Variant summary: COL4A3 c.4295G>A (p.Arg1432His) results in a non-conservative amino acid change located in the last collagen triple helix repeat (IPR008160) of 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 0.00038 in 280924 control chromosomes, predominantly at a frequency of 0.003 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL4A3 causing Alport Syndrome (autosomal recessive) phenotype (0.002), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.4295G>A in individuals affected with Alport Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc. RCV001276574 SCV001462973 likely benign Alport syndrome 3, autosomal dominant 2020-04-24 no assertion criteria provided clinical testing

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