chr2-227238007-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000091.5(COL4A3):c.127G>C(p.Gly43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,604,472 control chromosomes in the GnomAD database, including 97,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000091.5 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: 0.319 AC: 48484AN: 151848Hom.: 8194 Cov.: 31
GnomAD3 exomes AF: 0.284 AC: 70806AN: 249520Hom.: 11647 AF XY: 0.282 AC XY: 38196AN XY: 135370
GnomAD4 exome AF: 0.341 AC: 494969AN: 1452506Hom.: 89577 Cov.: 28 AF XY: 0.334 AC XY: 241510AN XY: 723070
GnomAD4 genome AF: 0.319 AC: 48521AN: 151966Hom.: 8201 Cov.: 31 AF XY: 0.309 AC XY: 22974AN XY: 74262
ClinVar
Submissions by phenotype
not specified Benign:8
Variant summary: The COL4A3 c.127G>C (p.Gly43Arg) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this variant. This variant was found in 34826/120756 control chromosomes (5825 homozygotes) at a frequency of 0.2883997, which is approximately 141 times the estimated maximal expected allele frequency of a pathogenic COL4A3 variant (0.0020412), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases/literature classified this variant as benign. Taken together, this variant is classified as benign. -
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p.Gly43Arg in exon 2 of COL4A3: This variant is not expected to have clinical si gnificance because it has been identified in 36.20% (24153/66730) of European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs13424243). -
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This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 29. Only high quality variants are reported. -
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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. -
not provided Benign:3
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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. -
Autosomal recessive Alport syndrome Benign:1
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Autosomal dominant Alport syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at