rs8063186

Positions:

• chr16-78951143-T-C
• chr16-78951143-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.1057-260465T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,072 control chromosomes in the GnomAD database, including 21,514 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 0.53 (21514 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-260465T>C		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-260465T>C		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-260465T>C		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80313 AN: 151954 Hom.: 21501 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.528 AC: 80367 AN: 152072 Hom.: 21514 Cov.: 32 AF XY: 0.526 AC XY: 39133 AN XY: 74350

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.552

Alfa AF: 0.524 Hom.: 20200

Bravo AF: 0.539

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
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: rs8063186; hg19: chr16-78985040;