rs2274159
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015404.4(WHRN):āc.2348T>Cā(p.Val783Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,610,410 control chromosomes in the GnomAD database, including 191,166 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_015404.4 missense
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WHRN | NM_015404.4 | c.2348T>C | p.Val783Ala | missense_variant | 10/12 | ENST00000362057.4 | NP_056219.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WHRN | ENST00000362057.4 | c.2348T>C | p.Val783Ala | missense_variant | 10/12 | 1 | NM_015404.4 | ENSP00000354623.3 |
Frequencies
GnomAD3 genomes AF: 0.414 AC: 62811AN: 151658Hom.: 14055 Cov.: 32
GnomAD3 exomes AF: 0.481 AC: 120111AN: 249582Hom.: 29689 AF XY: 0.489 AC XY: 65998AN XY: 135002
GnomAD4 exome AF: 0.490 AC: 714533AN: 1458632Hom.: 177104 Cov.: 74 AF XY: 0.493 AC XY: 357504AN XY: 725716
GnomAD4 genome AF: 0.414 AC: 62835AN: 151778Hom.: 14062 Cov.: 32 AF XY: 0.413 AC XY: 30639AN XY: 74164
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 29083408) - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 19, 2009 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive nonsyndromic hearing loss 31 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Usher syndrome type 2D Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at