rs2738572

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016373.4(WWOX):​c.1056+191583A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,878 control chromosomes in the GnomAD database, including 41,459 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 41459 hom., cov: 30)

Consequence

WWOX
NM_016373.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.805
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WWOXNM_016373.4 linkuse as main transcriptc.1056+191583A>C intron_variant ENST00000566780.6 NP_057457.1 Q9NZC7-1A0A411HBC7
WWOXNM_001291997.2 linkuse as main transcriptc.717+191583A>C intron_variant NP_001278926.1 Q9NZC7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WWOXENST00000566780.6 linkuse as main transcriptc.1056+191583A>C intron_variant 1 NM_016373.4 ENSP00000457230.1 Q9NZC7-1

Frequencies

GnomAD3 genomes
AF:
0.737
AC:
111833
AN:
151764
Hom.:
41419
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.794
Gnomad AMI
AF:
0.650
Gnomad AMR
AF:
0.730
Gnomad ASJ
AF:
0.762
Gnomad EAS
AF:
0.701
Gnomad SAS
AF:
0.660
Gnomad FIN
AF:
0.627
Gnomad MID
AF:
0.775
Gnomad NFE
AF:
0.729
Gnomad OTH
AF:
0.732
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.737
AC:
111919
AN:
151878
Hom.:
41459
Cov.:
30
AF XY:
0.731
AC XY:
54245
AN XY:
74174
show subpopulations
Gnomad4 AFR
AF:
0.795
Gnomad4 AMR
AF:
0.729
Gnomad4 ASJ
AF:
0.762
Gnomad4 EAS
AF:
0.701
Gnomad4 SAS
AF:
0.660
Gnomad4 FIN
AF:
0.627
Gnomad4 NFE
AF:
0.729
Gnomad4 OTH
AF:
0.728
Alfa
AF:
0.730
Hom.:
8195
Bravo
AF:
0.747
Asia WGS
AF:
0.651
AC:
2266
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
7.7
DANN
Benign
0.48

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.

Other links and lift over

dbSNP: rs2738572; hg19: chr16-78658232; API