rs11648482

chr16-78951176-G-Achr16-78951176-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016373.4(WWOX):c.1057-260432G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,172 control chromosomes in the GnomAD database, including 7,869 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 0.30 (7869 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-260432G>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-260432G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-260432G>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45502 AN: 152054 Hom.: 7871 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.299 AC: 45506 AN: 152172 Hom.: 7869 Cov.: 33 AF XY: 0.299 AC XY: 22281 AN XY: 74394

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.322

Alfa AF: 0.363 Hom.: 13563

Bravo AF: 0.290

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.073
Dann	Benign	0.63

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: rs11648482; hg19: chr16-78985073;