rs3751832

chr16-79180375-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016373.4(WWOX):c.1057-31233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,244 control chromosomes in the GnomAD database, including 1,325 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 0.11 (1325 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-31233A>G		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-31233A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-31233A>G		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17220 AN: 152126 Hom.: 1326 Cov.: 33

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.113 AC: 17215 AN: 152244 Hom.: 1325 Cov.: 33 AF XY: 0.119 AC XY: 8823 AN XY: 74426

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.116

Alfa AF: 0.112 Hom.: 1410

Bravo AF: 0.112

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	19
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs3751832; hg19: chr16-79214272;