chr2-227007466-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000092.5(COL4A4):c.4932C>T(p.Phe1644=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,613,496 control chromosomes in the GnomAD database, including 156,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. F1644F?) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000092.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A4 | NM_000092.5 | c.4932C>T | p.Phe1644= | synonymous_variant | 48/48 | ENST00000396625.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A4 | ENST00000396625.5 | c.4932C>T | p.Phe1644= | synonymous_variant | 48/48 | 5 | NM_000092.5 | P1 | |
COL4A4 | ENST00000682098.1 | c.534C>T | p.Phe178= | synonymous_variant | 3/3 |
Frequencies
GnomAD3 genomes AF: 0.479 AC: 72718AN: 151926Hom.: 17924 Cov.: 33
GnomAD3 exomes AF: 0.467 AC: 116579AN: 249438Hom.: 28005 AF XY: 0.465 AC XY: 62918AN XY: 135350
GnomAD4 exome AF: 0.431 AC: 629995AN: 1461452Hom.: 138410 Cov.: 65 AF XY: 0.434 AC XY: 315231AN XY: 727092
GnomAD4 genome AF: 0.479 AC: 72807AN: 152044Hom.: 17965 Cov.: 33 AF XY: 0.479 AC XY: 35588AN XY: 74310
ClinVar
Submissions by phenotype
not specified Benign:4
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 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | p.Phe1644Phe in exon 48 of COL4A4: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 63.69% (842/1322) of African chromosomes by the 1000 Genomes Project (Phase 3; dbSNP rs2228557). - |
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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 03, 2017 | - - |
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 12, 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 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at