16-78835648-C-T

Position:

• chr16-78835648-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.1057-375960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,094 control chromosomes in the GnomAD database, including 4,607 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 0.24 (4607 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-375960C>T		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-375960C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-375960C>T		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36936 AN: 151974 Hom.: 4605 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.243 AC: 36954 AN: 152094 Hom.: 4607 Cov.: 33 AF XY: 0.247 AC XY: 18342 AN XY: 74344

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.288

Alfa AF: 0.259 Hom.: 5074

Bravo AF: 0.240

Asia WGS AF: 0.261 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.051
DANN	Benign	0.59

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: rs4888855; hg19: chr16-78869545;