rs734312
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1
The NM_006005.3(WFS1):c.1832G>A(p.Arg611His) variant causes a missense change. The variant allele was found at a frequency of 0.533 in 1,613,864 control chromosomes in the GnomAD database, including 240,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R611Y) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006005.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.1832G>A | p.Arg611His | missense_variant | Exon 8 of 8 | ENST00000226760.5 | NP_005996.2 | |
WFS1 | NM_001145853.1 | c.1832G>A | p.Arg611His | missense_variant | Exon 8 of 8 | NP_001139325.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.432 AC: 65710AN: 152006Hom.: 17718 Cov.: 33
GnomAD3 exomes AF: 0.552 AC: 138753AN: 251300Hom.: 41050 AF XY: 0.557 AC XY: 75651AN XY: 135828
GnomAD4 exome AF: 0.544 AC: 794851AN: 1461740Hom.: 222427 Cov.: 97 AF XY: 0.546 AC XY: 396845AN XY: 727158
GnomAD4 genome AF: 0.432 AC: 65726AN: 152124Hom.: 17727 Cov.: 33 AF XY: 0.436 AC XY: 32442AN XY: 74346
ClinVar
Submissions by phenotype
not specified Benign:7
- -
- -
- -
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
- -
- -
- -
not provided Benign:4
- -
- -
This variant is associated with the following publications: (PMID: 24477584, 23257691, 30232070, 27398621, 10679252, 19328217, 17719176, 24464100, 23595122, 12707947) -
- -
Wolfram syndrome 1 Benign:2
Mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. rs734312 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained. -
- -
WFS1-Related Spectrum Disorders 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. -
Autosomal dominant nonsyndromic hearing loss 6 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