16-79025760-C-T

Position:

• chr16-79025760-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.1057-185848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 147,874 control chromosomes in the GnomAD database, including 16,324 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 0.46 (16324 hom., cov: 27)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-185848C>T		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-185848C>T		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-185848C>T		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 68508 AN: 147764 Hom.: 16319 Cov.: 27

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.463 AC: 68536 AN: 147874 Hom.: 16324 Cov.: 27 AF XY: 0.463 AC XY: 33242 AN XY: 71804

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.455

Alfa AF: 0.489 Hom.: 9142

Bravo AF: 0.470

Asia WGS AF: 0.494 AC: 1710 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.50

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: rs8053936; hg19: chr16-79059657;