rs11643794

Positions:

• chr16-78947457-G-A
• chr16-78947457-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.1057-264151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,102 control chromosomes in the GnomAD database, including 10,885 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 0.35 (10885 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-264151G>A		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-264151G>A		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-264151G>A		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52878 AN: 151984 Hom.: 10889 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.348 AC: 52874 AN: 152102 Hom.: 10885 Cov.: 33 AF XY: 0.353 AC XY: 26236 AN XY: 74360

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.379

Alfa AF: 0.391 Hom.: 3371

Bravo AF: 0.332

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.77

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: rs11643794; hg19: chr16-78981354;