NM_004385.5:c.5477G>A
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004385.5(VCAN):c.5477G>A(p.Arg1826His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,613,642 control chromosomes in the GnomAD database, including 117,577 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1826P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004385.5 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VCAN | NM_004385.5 | c.5477G>A | p.Arg1826His | missense_variant | Exon 8 of 15 | ENST00000265077.8 | NP_004376.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.382 AC: 58020AN: 151798Hom.: 11303 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.384 AC: 96019AN: 250096 AF XY: 0.378 show subpopulations
GnomAD4 exome AF: 0.379 AC: 554355AN: 1461726Hom.: 106270 Cov.: 74 AF XY: 0.376 AC XY: 273669AN XY: 727174 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.382 AC: 58041AN: 151916Hom.: 11307 Cov.: 32 AF XY: 0.380 AC XY: 28220AN XY: 74258 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Wagner syndrome Benign:3
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not specified Benign:2
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not provided Benign:2
This variant is associated with the following publications: (PMID: 19655167) -
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Vitreoretinopathy Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at