rs1862841

Positions:

• chr16-79014626-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.1057-196982A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,968 control chromosomes in the GnomAD database, including 12,909 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 0.40 (12909 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-196982A>T		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-196982A>T		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-196982A>T		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61409 AN: 151850 Hom.: 12888 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.405 AC: 61479 AN: 151968 Hom.: 12909 Cov.: 32 AF XY: 0.404 AC XY: 30012 AN XY: 74292

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.394

Alfa AF: 0.390 Hom.: 1524

Bravo AF: 0.421

Asia WGS AF: 0.408 AC: 1419 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	0.035
DANN	Benign	0.71

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: rs1862841; hg19: chr16-79048523;