NM_000091.4(COL4A3):c.4295G>A (p.Arg1432His) AND not specified

Clinical significance:Likely benign (Last evaluated: Feb 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001174854.1

Allele description [Variation Report for NM_000091.4(COL4A3):c.4295G>A (p.Arg1432His)]

NM_000091.4(COL4A3):c.4295G>A (p.Arg1432His)

Genes:
MFF-DT:MFF divergent transcript [Gene - HGNC]
COL4A3:collagen type IV alpha 3 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q36.3
Genomic location:
Preferred name:
NM_000091.4(COL4A3):c.4295G>A (p.Arg1432His)
HGVS:
  • NC_000002.12:g.227307752G>A
  • NG_011591.1:g.148188G>A
  • NM_000091.4:c.4295G>A
  • NP_000082.2:p.Arg1432His
  • LRG_230t1:c.4295G>A
  • LRG_230:g.148188G>A
  • LRG_230p1:p.Arg1432His
  • NC_000002.11:g.228172468G>A
Protein change:
R1432H
Links:
dbSNP: rs200509072
NCBI 1000 Genomes Browser:
rs200509072
Molecular consequence:
  • NM_000091.4:c.4295G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001338244Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Feb 3, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001338244.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 17, 2021

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