chr13-110307021-G-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001845.6(COL4A1):c.7C>A(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000663 in 1,464,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001845.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.7C>A | p.Pro3Thr | missense_variant | 1/52 | ENST00000375820.10 | |
COL4A1 | NM_001303110.2 | c.7C>A | p.Pro3Thr | missense_variant | 1/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820.10 | c.7C>A | p.Pro3Thr | missense_variant | 1/52 | 1 | NM_001845.6 | P1 | |
COL4A1 | ENST00000543140.6 | c.7C>A | p.Pro3Thr | missense_variant | 1/25 | 1 | |||
COL4A2 | ENST00000400163.7 | c.-44-839G>T | intron_variant | 5 | |||||
COL4A1 | ENST00000649738.1 | n.137C>A | non_coding_transcript_exon_variant | 1/31 |
Frequencies
GnomAD3 genomes AF: 0.000441 AC: 67AN: 152090Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000587 AC: 47AN: 80102Hom.: 0 AF XY: 0.000568 AC XY: 26AN XY: 45798
GnomAD4 exome AF: 0.000689 AC: 904AN: 1312428Hom.: 1 Cov.: 33 AF XY: 0.000675 AC XY: 436AN XY: 646298
GnomAD4 genome AF: 0.000440 AC: 67AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74402
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | COL4A1: BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 29, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2023 | Reported in an individual with pediatric arterial ischemic stroke in published literature (Grossi et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar (ClinVar Variant ID# 289628); This variant is associated with the following publications: (PMID: 32818659) - |
Brain small vessel disease 1 with or without ocular anomalies Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Apr 03, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Mar 26, 2019 | This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BS1,BP4. - |
Schizencephaly;C0423401:Retinal arterial tortuosity;C2673195:Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome;C3281105:Hemorrhage, intracerebral, susceptibility to;C4551998:Brain small vessel disease 1 with or without ocular anomalies Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Mar 26, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at