rs5024396

Variant names:

• chr16-78968295-G-A
• rs5024396
• NM_016373.4:c.1057-243313G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-78968295-G-A
• chr16-78968295-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.1057-243313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,086 control chromosomes in the GnomAD database, including 14,997 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 0.44 (14997 hom., cov: 34)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 2 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWOX	NM_016373.4	MANE Select	c.1057-243313G>A		intron	N/A	NP_057457.1	Q9NZC7-1
	WWOX	NM_001291997.2		c.718-243313G>A		intron	N/A	NP_001278926.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWOX	ENST00000566780.6	TSL:1 MANE Select	c.1057-243313G>A		intron	N/A	ENSP00000457230.1	Q9NZC7-1
	WWOX	ENST00000402655.6	TSL:1	c.410-243313G>A		intron	N/A	ENSP00000384238.2	Q9NZC7-6
	WWOX	ENST00000406884.6	TSL:1	c.517-243313G>A		intron	N/A	ENSP00000384495.2	Q9NZC7-5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66148 AN: 151968 Hom.: 14994 Cov.: 34

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.435 AC: 66198 AN: 152086 Hom.: 14997 Cov.: 34 AF XY: 0.430 AC XY: 31955 AN XY: 74340

African (AFR) AF: 0.478 AC: 19848 AN: 41482

American (AMR) AF: 0.347 AC: 5304 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3464

East Asian (EAS) AF: 0.0849 AC: 438 AN: 5156

South Asian (SAS) AF: 0.327 AC: 1576 AN: 4820

European-Finnish (FIN) AF: 0.480 AC: 5073 AN: 10578

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31572 AN: 67990

Other (OTH) AF: 0.418 AC: 883 AN: 2110

Alfa AF: 0.340 Hom.: 955

Bravo AF: 0.424

Asia WGS AF: 0.230 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.61
PhyloP100		-0.078
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: rs5024396; hg19: chr16-79002192;