rs17706989

chr16-78536060-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016373.4(WWOX):c.1056+103308C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,166 control chromosomes in the GnomAD database, including 70 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 0.026 (70 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0256 (3891/152166) while in subpopulation NFE AF= 0.0401 (2726/68004). AF 95% confidence interval is 0.0388. There are 70 homozygotes in gnomad4. There are 1828 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 70 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1056+103308C>G		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.717+103308C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+103308C>G		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3889 AN: 152048 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.00773

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0256 AC: 3891 AN: 152166 Hom.: 70 Cov.: 32 AF XY: 0.0246 AC XY: 1828 AN XY: 74386

Gnomad4 AFR AF: 0.00773

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0245

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0347 Hom.: 42

Bravo AF: 0.0250

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.0
Dann	Benign	0.48

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: rs17706989; hg19: chr16-78569957;