rs9319530

Positions:

• chr16-78957681-C-G
• chr16-78957681-C-T

Variant summary

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

The NM_016373.4(WWOX):​c.1057-253927C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,152 control chromosomes in the GnomAD database, including 22,438 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 0.54 (22438 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

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=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-253927C>G		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-253927C>G		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-253927C>G		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81421 AN: 152034 Hom.: 22433 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.535 AC: 81468 AN: 152152 Hom.: 22438 Cov.: 33 AF XY: 0.539 AC XY: 40080 AN XY: 74374

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.567

Alfa AF: 0.509 Hom.: 2483

Bravo AF: 0.549

Asia WGS AF: 0.740 AC: 2570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.77

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: rs9319530; hg19: chr16-78991578;