rs11150119

Variant names:

• chr16-78957146-G-A
• rs11150119
• NM_016373.4:c.1057-254462G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-78957146-G-A
• chr16-78957146-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.1057-254462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,978 control chromosomes in the GnomAD database, including 22,779 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 0.54 (22779 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-254462G>A		intron_variant	Intron 8 of 8	ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-254462G>A		intron_variant	Intron 7 of 7		NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-254462G>A		intron_variant	Intron 8 of 8	1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82071 AN: 151862 Hom.: 22764 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.540 AC: 82139 AN: 151978 Hom.: 22779 Cov.: 32 AF XY: 0.544 AC XY: 40419 AN XY: 74266

African (AFR) AF: 0.562 AC: 23296 AN: 41444

American (AMR) AF: 0.592 AC: 9037 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3468

East Asian (EAS) AF: 0.872 AC: 4505 AN: 5166

South Asian (SAS) AF: 0.614 AC: 2950 AN: 4808

European-Finnish (FIN) AF: 0.448 AC: 4732 AN: 10558

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33533 AN: 67944

Other (OTH) AF: 0.556 AC: 1172 AN: 2108

Alfa AF: 0.516 Hom.: 26041

Bravo AF: 0.554

Asia WGS AF: 0.721 AC: 2503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.50
PhyloP100		0.067
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: rs11150119; hg19: chr16-78991043;