rs8047597

Positions:

• chr16-79022859-A-G
• chr16-79022859-A-T

Variant summary

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

The NM_016373.4(WWOX):​c.1057-188749A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,958 control chromosomes in the GnomAD database, including 19,342 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 0.50 (19342 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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 (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-188749A>G		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-188749A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-188749A>G		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75841 AN: 151838 Hom.: 19339 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.499 AC: 75863 AN: 151958 Hom.: 19342 Cov.: 32 AF XY: 0.496 AC XY: 36860 AN XY: 74244

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.505

Alfa AF: 0.524 Hom.: 10799

Bravo AF: 0.503

Asia WGS AF: 0.508 AC: 1765 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	0.025
DANN	Benign	0.76

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: rs8047597; hg19: chr16-79056756;