Variant 16-78624496-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_016373.4(WWOX):c.1056+191744T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,036 control chromosomes in the GnomAD database, including 22,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22006 hom., cov: 32)

Consequence

WWOX
NM_016373.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.74

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 16-78624496-T-G is Benign according to our data. Variant chr16-78624496-T-G is described in ClinVar as [Benign]. Clinvar id is 540240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4 linkuse as main transcript	c.1056+191744T>G		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2 linkuse as main transcript	c.717+191744T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6 linkuse as main transcript	c.1056+191744T>G		intron_variant		1	NM_016373.4	P1	Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79641

AN:

151918

Hom.:

21998

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.524

AC:

79680

AN:

152036

Hom.:

22006

Cov.:

AF XY:

0.521

AC XY:

38717

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.616

Gnomad4 ASJ

AF:

0.622

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.488

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.593

Hom.:

52496

Bravo

AF:

0.528

Asia WGS

AF:

0.521

AC:

1811

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2020

This variant is associated with the following publications: (PMID: 23197378, 18674750) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over