16-78918542-A-G

Position:

• chr16-78918542-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.1057-293066A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,012 control chromosomes in the GnomAD database, including 65,064 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 0.92 (65064 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1057-293066A>G		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.718-293066A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-293066A>G		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139637 AN: 151892 Hom.: 65033 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.971

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.919 AC: 139716 AN: 152012 Hom.: 65064 Cov.: 32 AF XY: 0.921 AC XY: 68396 AN XY: 74292

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 0.981

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.942

Alfa AF: 0.983 Hom.: 100487

Bravo AF: 0.908

Asia WGS AF: 0.961 AC: 3343 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	0.016
DANN	Benign	0.21

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: rs9923451; hg19: chr16-78952439;