rs11150069

Positions:

• chr16-78373166-A-C
• chr16-78373166-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.517-13694A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,952 control chromosomes in the GnomAD database, including 33,584 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 0.65 (33584 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.517-13694A>C		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.178-13694A>C		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.517-13694A>C		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98753 AN: 151832 Hom.: 33559 Cov.: 31

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.650 AC: 98819 AN: 151952 Hom.: 33584 Cov.: 31 AF XY: 0.641 AC XY: 47610 AN XY: 74278

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.0710

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.637

Alfa AF: 0.679 Hom.: 10746

Bravo AF: 0.641

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.36

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: rs11150069; hg19: chr16-78407063;