2-227022057-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000092.5(COL4A4):c.4207T>C(p.Ser1403Pro) variant causes a missense change. The variant allele was found at a frequency of 0.447 in 1,612,828 control chromosomes in the GnomAD database, including 164,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.494 AC: 74967AN: 151788Hom.: 19134 Cov.: 31
GnomAD3 exomes AF: 0.477 AC: 118999AN: 249310Hom.: 29113 AF XY: 0.473 AC XY: 64022AN XY: 135304
GnomAD4 exome AF: 0.442 AC: 645388AN: 1460922Hom.: 145151 Cov.: 38 AF XY: 0.443 AC XY: 322051AN XY: 726778
GnomAD4 genome AF: 0.494 AC: 75056AN: 151906Hom.: 19177 Cov.: 31 AF XY: 0.494 AC XY: 36664AN XY: 74228
ClinVar
Submissions by phenotype
not specified Benign:5
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p.Ser1403Pro in exon 44 of COL4A4: This variant is not expected to have clinical significance because it has been identified in 68.91% (911/1322) of African chr omosomes by the 1000 Genomes Project (Phase 3; dbSNP rs3752895). -
This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 65. Only high quality variants are reported. -
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
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. -
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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