rs12716852

Variant names:

• chr16-78154841-G-A
• rs12716852
• NM_016373.4:c.410-9342G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-78154841-G-A
• chr16-78154841-G-C
• chr16-78154841-G-T

Variant summary

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

The NM_016373.4(WWOX):​c.410-9342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,850 control chromosomes in the GnomAD database, including 24,693 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 0.57 (24693 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4	c.410-9342G>A		intron_variant	Intron 4 of 8	ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.71-9342G>A		intron_variant	Intron 3 of 7		NP_001278926.1
WWOX	NM_130791.5	c.410-9342G>A		intron_variant	Intron 4 of 5		NP_570607.1
WWOX	NR_120436.3	n.649-9342G>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.410-9342G>A		intron_variant	Intron 4 of 8	1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86164 AN: 151732 Hom.: 24673 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.568 AC: 86231 AN: 151850 Hom.: 24693 Cov.: 31 AF XY: 0.564 AC XY: 41900 AN XY: 74230

African (AFR) AF: 0.646 AC: 26743 AN: 41380

American (AMR) AF: 0.535 AC: 8159 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2608 AN: 5132

South Asian (SAS) AF: 0.500 AC: 2413 AN: 4828

European-Finnish (FIN) AF: 0.545 AC: 5739 AN: 10536

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36924 AN: 67934

Other (OTH) AF: 0.551 AC: 1162 AN: 2110

Alfa AF: 0.548 Hom.: 45748

Bravo AF: 0.571

Asia WGS AF: 0.499 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.10
DANN	Benign	0.58
PhyloP100		-1.4
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: rs12716852; hg19: chr16-78188738;