chr16-78972966-G-A

Position:

• chr16-78972966-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.1057-238642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,118 control chromosomes in the GnomAD database, including 55,441 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 0.85 (55441 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-238642G>A		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-238642G>A		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-238642G>A		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128483 AN: 152000 Hom.: 55414 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.845 AC: 128554 AN: 152118 Hom.: 55441 Cov.: 31 AF XY: 0.844 AC XY: 62767 AN XY: 74348

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.990

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.875

Alfa AF: 0.908 Hom.: 37684

Bravo AF: 0.830

Asia WGS AF: 0.849 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.86

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: rs10492908; hg19: chr16-79006863;