16-78360143-A-G

Position:

• chr16-78360143-A-G

Variant summary

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

The NM_016373.4(WWOX):​c.517-26717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,034 control chromosomes in the GnomAD database, including 22,575 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 0.53 (22575 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.517-26717A>G		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.178-26717A>G		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.517-26717A>G		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80099 AN: 151916 Hom.: 22571 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.527 AC: 80122 AN: 152034 Hom.: 22575 Cov.: 32 AF XY: 0.522 AC XY: 38768 AN XY: 74322

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.0718

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.523

Alfa AF: 0.584 Hom.: 3286

Bravo AF: 0.512

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.45

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: rs4888786; hg19: chr16-78394040;