rs4888865

chr16-78843521-C-Achr16-78843521-C-G

Variant summary

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

The NM_016373.4(WWOX):c.1057-368087C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 149,340 control chromosomes in the GnomAD database, including 42,136 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 0.73 (42136 hom., cov: 30)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-368087C>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-368087C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-368087C>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 109278 AN: 149220 Hom.: 42115 Cov.: 30

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.732 AC: 109344 AN: 149340 Hom.: 42136 Cov.: 30 AF XY: 0.732 AC XY: 53269 AN XY: 72810

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.750

Alfa AF: 0.777 Hom.: 33768

Asia WGS AF: 0.603 AC: 2082 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.46
Dann	Benign	0.37

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: rs4888865; hg19: chr16-78877418;