16-78730200-T-C

Variant summary

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

The NM_016373.4(WWOX):c.1056+297448T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,952 control chromosomes in the GnomAD database, including 8,797 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 0.34 (8797 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1056+297448T>C		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.717+297448T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+297448T>C		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50879 AN: 151834 Hom.: 8777 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.335 AC: 50946 AN: 151952 Hom.: 8797 Cov.: 32 AF XY: 0.335 AC XY: 24852 AN XY: 74294

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.328

Alfa AF: 0.265 Hom.: 1390

Bravo AF: 0.335

Asia WGS AF: 0.455 AC: 1582 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.3
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: rs8047442; hg19: chr16-78764097;