rs1110894

Positions:

• chr16-78971854-T-C
• chr16-78971854-T-G

Variant summary

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

The NM_016373.4(WWOX):​c.1057-239754T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,920 control chromosomes in the GnomAD database, including 38,377 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 0.70 (38377 hom., cov: 30)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-239754T>C		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-239754T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-239754T>C		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106571 AN: 151802 Hom.: 38347 Cov.: 30

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.702 AC: 106656 AN: 151920 Hom.: 38377 Cov.: 30 AF XY: 0.698 AC XY: 51785 AN XY: 74216

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.687

Alfa AF: 0.648 Hom.: 40326

Bravo AF: 0.711

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.60

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: rs1110894; hg19: chr16-79005751;