rs4130513

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016373.4(WWOX):c.606-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,034 control chromosomes in the GnomAD database, including 20,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 8191 hom., cov: 32)

Exomes 𝑓: 0.094 ( 12417 hom. )

Consequence

WWOX
NM_016373.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.510

Publications

11 publications found

Variant links:

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]

WWOX Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive spinocerebellar ataxia 12
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
developmental and epileptic encephalopathy, 28
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
46,XY partial gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WWOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-78424853-G-A is Benign according to our data. Variant chr16-78424853-G-A is described in ClinVar as [Benign]. Clinvar id is 260742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4 link	c.606-17G>A		intron_variant	Intron 6 of 8	ENST00000566780.6	NP_057457.1	Q9NZC7-1A0A411HBC7
WWOX	NM_001291997.2 link	c.267-17G>A		intron_variant	Intron 5 of 7		NP_001278926.1	Q9NZC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6 link	c.606-17G>A		intron_variant	Intron 6 of 8	1	NM_016373.4	ENSP00000457230.1		Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35326

AN:

151846

Hom.:

8161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0906

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.190

GnomAD2 exomes

AF:

0.133

AC:

33197

AN:

248764

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.614

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.0905

Gnomad NFE exome

AF:

0.0721

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.0939

AC:

137157

AN:

1461070

Hom.:

12417

Cov.:

AF XY:

0.0937

AC XY:

68082

AN XY:

726920

show subpopulations

African (AFR)

AF:

0.625

AC:

20800

AN:

33306

American (AMR)

AF:

0.120

AC:

5366

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

3483

AN:

26134

East Asian (EAS)

AF:

0.169

AC:

6716

AN:

39688

South Asian (SAS)

AF:

0.146

AC:

12566

AN:

86230

European-Finnish (FIN)

AF:

0.0926

AC:

4947

AN:

53400

Middle Eastern (MID)

AF:

0.137

AC:

792

AN:

5764

European-Non Finnish (NFE)

AF:

0.0674

AC:

74968

AN:

1111480

Other (OTH)

AF:

0.125

AC:

7519

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

6017

12033

18050

24066

30083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.233

AC:

35408

AN:

151964

Hom.:

8191

Cov.:

AF XY:

0.231

AC XY:

17144

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.601

AC:

24859

AN:

41382

American (AMR)

AF:

0.143

AC:

2189

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

449

AN:

3468

East Asian (EAS)

AF:

0.187

AC:

967

AN:

5160

South Asian (SAS)

AF:

0.150

AC:

722

AN:

4812

European-Finnish (FIN)

AF:

0.0906

AC:

959

AN:

10586

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0706

AC:

4798

AN:

67980

Other (OTH)

AF:

0.188

AC:

397

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

965

1930

2896

3861

4826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.119

Hom.:

3324

Bravo

AF:

0.251

Asia WGS

AF:

0.205

AC:

717

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 21. Only high quality variants are reported. -

Jan 12, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.88

(source)

DANN

Benign

0.45

PhyloP100

-0.51

PromoterAI

-0.0052

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs4130513

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over