rs1079569

Variant names:

• chr16-78124682-G-A
• rs1079569
• NM_016373.4:c.409+9528G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-78124682-G-A
• chr16-78124682-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016373.4(WWOX):​c.409+9528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,088 control chromosomes in the GnomAD database, including 33,750 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 0.67 (33750 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 4 publications found

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]

WWOX Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive spinocerebellar ataxia 12

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• developmental and epileptic encephalopathy, 28

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWOX	NM_016373.4	MANE Select	c.409+9528G>A		intron	N/A	NP_057457.1
	WWOX	NM_001291997.2		c.70+9528G>A		intron	N/A	NP_001278926.1
	WWOX	NM_130791.5		c.409+9528G>A		intron	N/A	NP_570607.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWOX	ENST00000566780.6	TSL:1 MANE Select	c.409+9528G>A		intron	N/A	ENSP00000457230.1
	WWOX	ENST00000408984.7	TSL:1	c.409+9528G>A		intron	N/A	ENSP00000386161.3
	WWOX	ENST00000402655.6	TSL:1	c.409+9528G>A		intron	N/A	ENSP00000384238.2

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101127 AN: 151970 Hom.: 33708 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.666 AC: 101227 AN: 152088 Hom.: 33750 Cov.: 33 AF XY: 0.663 AC XY: 49296 AN XY: 74354

African (AFR) AF: 0.685 AC: 28413 AN: 41456

American (AMR) AF: 0.665 AC: 10170 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2326 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3770 AN: 5168

South Asian (SAS) AF: 0.583 AC: 2812 AN: 4822

European-Finnish (FIN) AF: 0.656 AC: 6937 AN: 10570

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44618 AN: 67992

Other (OTH) AF: 0.665 AC: 1405 AN: 2114

Alfa AF: 0.662 Hom.: 15526

Bravo AF: 0.668

Asia WGS AF: 0.635 AC: 2210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.40
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1079569; hg19: chr16-78158579;