rs8052893

Positions:

• chr16-78965652-G-A

Variant summary

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

The ENST00000566780.6(WWOX):​c.1057-245956G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,622 control chromosomes in the GnomAD database, including 14,384 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 0.43 (14384 hom., cov: 31)
• Consequence: WWOX ENST00000566780.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-245956G>A		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-245956G>A		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-245956G>A		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64544 AN: 151514 Hom.: 14379 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.0877

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.426 AC: 64593 AN: 151622 Hom.: 14384 Cov.: 31 AF XY: 0.420 AC XY: 31121 AN XY: 74068

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.0881

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.413

Alfa AF: 0.447 Hom.: 3135

Bravo AF: 0.413

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.080
DANN	Benign	0.55

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: rs8052893; hg19: chr16-78999549;