rs8050128
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000566780.6(WWOX):c.517-108260C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,581,356 control chromosomes in the GnomAD database, including 166,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.47 ( 16822 hom., cov: 32)
Exomes 𝑓: 0.45 ( 149745 hom. )
Consequence
WWOX
ENST00000566780.6 intron
ENST00000566780.6 intron
Scores
2
Splicing: ADA: 0.00002942
2
Clinical Significance
Conservation
PhyloP100: 0.736
Genes affected
WWOX (HGNC:12799): (WW domain containing oxidoreductase) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 16-78278600-C-A is Benign according to our data. Variant chr16-78278600-C-A is described in ClinVar as [Benign]. Clinvar id is 586944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-78278600-C-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.517-108260C>A | intron_variant | ENST00000566780.6 | NP_057457.1 | |||
WWOX | NM_001291997.2 | c.178-108260C>A | intron_variant | NP_001278926.1 | ||||
WWOX | NM_130791.5 | c.517-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_570607.1 | ||||
WWOX | NR_120436.3 | n.756-3C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WWOX | ENST00000566780.6 | c.517-108260C>A | intron_variant | 1 | NM_016373.4 | ENSP00000457230 | P1 |
Frequencies
GnomAD3 genomes AF: 0.467 AC: 70874AN: 151814Hom.: 16799 Cov.: 32
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GnomAD3 exomes AF: 0.449 AC: 109000AN: 242750Hom.: 24955 AF XY: 0.446 AC XY: 58704AN XY: 131484
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GnomAD4 exome AF: 0.451 AC: 644353AN: 1429424Hom.: 149745 Cov.: 34 AF XY: 0.449 AC XY: 319603AN XY: 711194
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GnomAD4 genome AF: 0.467 AC: 70939AN: 151932Hom.: 16822 Cov.: 32 AF XY: 0.464 AC XY: 34454AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 33. Only high quality variants are reported. - |
WWOX-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at