4-6291182-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006005.3(WFS1):c.461-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,502 control chromosomes in the GnomAD database, including 30,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_006005.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.461-15C>T | intron_variant | Intron 4 of 7 | ENST00000226760.5 | NP_005996.2 | ||
WFS1 | NM_001145853.1 | c.461-15C>T | intron_variant | Intron 4 of 7 | NP_001139325.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.630 AC: 95323AN: 151384Hom.: 30570 Cov.: 31
GnomAD3 exomes AF: 0.658 AC: 163193AN: 248086Hom.: 54739 AF XY: 0.656 AC XY: 88080AN XY: 134344
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.620 AC: 903560AN: 1456244Hom.: 284228 Cov.: 48 AF XY: 0.622 AC XY: 450961AN XY: 724520
GnomAD4 genome AF: 0.630 AC: 95409AN: 151502Hom.: 30608 Cov.: 31 AF XY: 0.632 AC XY: 46777AN XY: 74012
ClinVar
Submissions by phenotype
not specified Benign:6
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461-15C>T in Intron 04 of WFS1: This variant is not expected to have clinical si gnificance because it has been identified in 38.9% (2732/7020) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs9998519). -
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not provided Benign:3
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WFS1-Related Spectrum Disorders Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Autosomal dominant nonsyndromic hearing loss 6 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Wolfram syndrome 1 Benign:1
Mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. rs9998519 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at