rs17709147

chr16-78956689-T-Achr16-78956689-T-G

Variant summary

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

The NM_016373.4(WWOX):c.1057-254919T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 152,272 control chromosomes in the GnomAD database, including 458 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 0.067 (458 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-254919T>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-254919T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-254919T>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10147 AN: 152154 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0666 AC: 10140 AN: 152272 Hom.: 458 Cov.: 32 AF XY: 0.0630 AC XY: 4689 AN XY: 74462

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.0819

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0566

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0368 Hom.: 32

Bravo AF: 0.0660

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.7
Dann	Benign	0.72

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: rs17709147; hg19: chr16-78990586;