rs9646322

chr16-79130954-G-Achr16-79130954-G-C

Variant summary

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

The NM_016373.4(WWOX):c.1057-80654G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,128 control chromosomes in the GnomAD database, including 6,357 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 0.27 (6357 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-80654G>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-80654G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-80654G>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41198 AN: 152010 Hom.: 6346 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.271 AC: 41251 AN: 152128 Hom.: 6357 Cov.: 33 AF XY: 0.271 AC XY: 20178 AN XY: 74352

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.280

Alfa AF: 0.212 Hom.: 6016

Bravo AF: 0.282

Asia WGS AF: 0.348 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.036
Dann	Benign	0.41

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: rs9646322; hg19: chr16-79164851;