rs1467067

chr16-78970586-A-Cchr16-78970586-A-G

Variant summary

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

The NM_016373.4(WWOX):c.1057-241022A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,176 control chromosomes in the GnomAD database, including 4,364 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 0.22 (4364 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-241022A>C		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-241022A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-241022A>C		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34167 AN: 152058 Hom.: 4367 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.224 AC: 34163 AN: 152176 Hom.: 4364 Cov.: 32 AF XY: 0.218 AC XY: 16242 AN XY: 74382

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.213

Alfa AF: 0.271 Hom.: 6140

Bravo AF: 0.216

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.8
Dann	Benign	0.66

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: rs1467067; hg19: chr16-79004483;