rs12931172

Variant names:

• chr16-78104193-G-C
• rs12931172
• NM_016373.4:c.108-4230G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-78104193-G-C
• chr16-78104193-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.108-4230G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 149,662 control chromosomes in the GnomAD database, including 7,388 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 0.32 (7388 hom., cov: 27)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.67
• Publications: 6 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=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4	c.108-4230G>C		intron_variant	Intron 1 of 8	ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.-168+4308G>C		intron_variant	Intron 1 of 7		NP_001278926.1
WWOX	NM_130791.5	c.108-4230G>C		intron_variant	Intron 1 of 5		NP_570607.1
WWOX	NR_120436.3	n.346+4194G>C		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.108-4230G>C		intron_variant	Intron 1 of 8	1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47189 AN: 149540 Hom.: 7374 Cov.: 27

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.316 AC: 47243 AN: 149662 Hom.: 7388 Cov.: 27 AF XY: 0.314 AC XY: 22907 AN XY: 72848

African (AFR) AF: 0.339 AC: 13719 AN: 40466

American (AMR) AF: 0.267 AC: 4011 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1198 AN: 3452

East Asian (EAS) AF: 0.220 AC: 1099 AN: 4990

South Asian (SAS) AF: 0.252 AC: 1192 AN: 4732

European-Finnish (FIN) AF: 0.354 AC: 3581 AN: 10108

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.318 AC: 21493 AN: 67598

Other (OTH) AF: 0.287 AC: 600 AN: 2090

Alfa AF: 0.314 Hom.: 935

Bravo AF: 0.311

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.019
DANN	Benign	0.32
PhyloP100		-4.7
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: rs12931172; hg19: chr16-78138090;