rs8047300

Positions:

• chr16-79023052-C-A

Variant summary

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

The NM_016373.4(WWOX):​c.1057-188556C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 149,200 control chromosomes in the GnomAD database, including 40,242 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 0.74 (40242 hom., cov: 30)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-188556C>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-188556C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-188556C>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 110116 AN: 149100 Hom.: 40214 Cov.: 30

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.739 AC: 110191 AN: 149200 Hom.: 40242 Cov.: 30 AF XY: 0.733 AC XY: 53496 AN XY: 72934

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.745

Alfa AF: 0.702 Hom.: 29262

Bravo AF: 0.742

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.086
DANN	Benign	0.31

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: rs8047300; hg19: chr16-79056949;