chr13-110306972-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4BS1_SupportingBS2_Supporting
The NM_001845.6(COL4A1):c.56A>T(p.His19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,475,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Consequence
NM_001845.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A1 | NM_001845.6 | c.56A>T | p.His19Leu | missense_variant | 1/52 | ENST00000375820.10 | |
COL4A1 | NM_001303110.2 | c.56A>T | p.His19Leu | missense_variant | 1/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A1 | ENST00000375820.10 | c.56A>T | p.His19Leu | missense_variant | 1/52 | 1 | NM_001845.6 | P1 | |
COL4A1 | ENST00000543140.6 | c.56A>T | p.His19Leu | missense_variant | 1/25 | 1 | |||
COL4A2 | ENST00000400163.7 | c.-44-888T>A | intron_variant | 5 | |||||
COL4A1 | ENST00000649738.1 | n.186A>T | non_coding_transcript_exon_variant | 1/31 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151956Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000237 AC: 2AN: 84556Hom.: 0 AF XY: 0.0000209 AC XY: 1AN XY: 47944
GnomAD4 exome AF: 0.00000302 AC: 4AN: 1323664Hom.: 0 Cov.: 30 AF XY: 0.00000307 AC XY: 2AN XY: 652128
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152064Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 19 of the COL4A1 protein (p.His19Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1495098). 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 with a negative predictive value of 95%. 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