rs2229814
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000092.5(COL4A4):c.1444C>T(p.Pro482Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,610,152 control chromosomes in the GnomAD database, including 212,777 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A4 | NM_000092.5 | c.1444C>T | p.Pro482Ser | missense_variant | 21/48 | ENST00000396625.5 | NP_000083.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A4 | ENST00000396625.5 | c.1444C>T | p.Pro482Ser | missense_variant | 21/48 | 5 | NM_000092.5 | ENSP00000379866 | P1 |
Frequencies
GnomAD3 genomes AF: 0.513 AC: 77589AN: 151114Hom.: 19978 Cov.: 29
GnomAD3 exomes AF: 0.540 AC: 134535AN: 249218Hom.: 37133 AF XY: 0.538 AC XY: 72729AN XY: 135214
GnomAD4 exome AF: 0.511 AC: 745448AN: 1458914Hom.: 192777 Cov.: 37 AF XY: 0.513 AC XY: 372545AN XY: 725928
GnomAD4 genome AF: 0.514 AC: 77667AN: 151238Hom.: 20000 Cov.: 29 AF XY: 0.516 AC XY: 38123AN XY: 73820
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 68. Only high quality variants are reported. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | p.Pro482Ser in exon 21 of COL4A4: This variant is not expected to have clinical significance because it has been identified in 68.08% (7860/11546) of Latino chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs2229814). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | 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. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Alport syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at