rs4888846

Positions:

• chr16-78771866-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016373.4(WWOX):​c.1056+339114A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,840 control chromosomes in the GnomAD database, including 7,794 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 0.31 (7794 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1056+339114A>T		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.717+339114A>T		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+339114A>T		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47105 AN: 151730 Hom.: 7779 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.311 AC: 47147 AN: 151840 Hom.: 7794 Cov.: 31 AF XY: 0.304 AC XY: 22597 AN XY: 74242

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.0879

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.305

Alfa AF: 0.323 Hom.: 760

Bravo AF: 0.304

Asia WGS AF: 0.257 AC: 890 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0060
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs4888846; hg19: chr16-78805763;