rs16949276

chr16-79027865-G-Achr16-79027865-G-T

Variant summary

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

The NM_016373.4(WWOX):c.1057-183743G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 151,836 control chromosomes in the GnomAD database, including 1,637 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 0.13 (1637 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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 = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-183743G>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-183743G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-183743G>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20121 AN: 151716 Hom.: 1625 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.133 AC: 20159 AN: 151836 Hom.: 1637 Cov.: 32 AF XY: 0.135 AC XY: 10006 AN XY: 74252

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.151

Alfa AF: 0.120 Hom.: 1137

Bravo AF: 0.127

Asia WGS AF: 0.128 AC: 447 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	0.62
Dann	Benign	0.44

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: rs16949276; hg19: chr16-79061762;