chr16-78967026-G-A

Position:

• chr16-78967026-G-A

Variant summary

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

The NM_016373.4(WWOX):​c.1057-244582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,906 control chromosomes in the GnomAD database, including 14,558 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 0.43 (14558 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-244582G>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-244582G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-244582G>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65109 AN: 151790 Hom.: 14555 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.429 AC: 65158 AN: 151906 Hom.: 14558 Cov.: 31 AF XY: 0.424 AC XY: 31452 AN XY: 74250

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.412

Alfa AF: 0.313 Hom.: 826

Bravo AF: 0.417

Asia WGS AF: 0.227 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.033
DANN	Benign	0.43

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: rs13339083; hg19: chr16-79000923;