rs35998949
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000092.5(COL4A4):c.1781A>G(p.Glu594Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,614,088 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000092.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0209 AC: 3181AN: 152102Hom.: 112 Cov.: 32
GnomAD3 exomes AF: 0.00521 AC: 1301AN: 249558Hom.: 37 AF XY: 0.00402 AC XY: 544AN XY: 135396
GnomAD4 exome AF: 0.00215 AC: 3137AN: 1461868Hom.: 119 Cov.: 31 AF XY: 0.00187 AC XY: 1361AN XY: 727230
GnomAD4 genome AF: 0.0210 AC: 3193AN: 152220Hom.: 112 Cov.: 32 AF XY: 0.0204 AC XY: 1521AN XY: 74428
ClinVar
Submissions by phenotype
not specified Benign:5
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p.Glu594Gly in exon 24 of COL4A4: This variant is not expected to have clinical significance because it has been identified in 7.24% (709/9798) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35998949). -
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. -
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Alport syndrome Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
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Kidney disorder Benign:1
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Autosomal recessive Alport syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at