rs4888892

Positions:

• chr16-78967094-C-G
• chr16-78967094-C-T

Variant summary

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

The NM_016373.4(WWOX):​c.1057-244514C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,912 control chromosomes in the GnomAD database, including 8,720 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 0.31 (8720 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-244514C>G		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-244514C>G		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-244514C>G		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46385 AN: 151794 Hom.: 8721 Cov.: 31

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.305 AC: 46381 AN: 151912 Hom.: 8720 Cov.: 31 AF XY: 0.308 AC XY: 22888 AN XY: 74220

Gnomad4 AFR AF: 0.0802

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.310

Alfa AF: 0.220 Hom.: 593

Bravo AF: 0.289

Asia WGS AF: 0.253 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4888892; hg19: chr16-79000991;