chr13-110306954-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001845.6(COL4A1):āc.74C>Gā(p.Ala25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,322,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. A25A) has been classified as Likely benign.
Frequency
Consequence
NM_001845.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.74C>G | p.Ala25Gly | missense_variant | 1/52 | ENST00000375820.10 | |
COL4A1 | NM_001303110.2 | c.74C>G | p.Ala25Gly | missense_variant | 1/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820.10 | c.74C>G | p.Ala25Gly | missense_variant | 1/52 | 1 | NM_001845.6 | P1 | |
COL4A1 | ENST00000543140.6 | c.74C>G | p.Ala25Gly | missense_variant | 1/25 | 1 | |||
COL4A2 | ENST00000400163.7 | c.-44-906G>C | intron_variant | 5 | |||||
COL4A1 | ENST00000649738.1 | n.204C>G | non_coding_transcript_exon_variant | 1/31 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 1AN: 84302Hom.: 0 AF XY: 0.0000209 AC XY: 1AN XY: 47772
GnomAD4 exome AF: 0.00000151 AC: 2AN: 1322156Hom.: 0 Cov.: 30 AF XY: 0.00000307 AC XY: 2AN XY: 651042
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 22, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 25 of the COL4A1 protein (p.Ala25Gly). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL4A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at