chr16-79016219-C-T

Position:

• chr16-79016219-C-T

Variant summary

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

The NM_016373.4(WWOX):​c.1057-195389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,128 control chromosomes in the GnomAD database, including 2,352 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 0.16 (2352 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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]

ENSG00000280274 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-195389C>T		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-195389C>T		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-195389C>T		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24888 AN: 152006 Hom.: 2343 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24915 AN: 152124 Hom.: 2352 Cov.: 33 AF XY: 0.170 AC XY: 12609 AN XY: 74350

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.161

Alfa AF: 0.149 Hom.: 2583

Bravo AF: 0.164

Asia WGS AF: 0.350 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.28

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: rs16949222; hg19: chr16-79050116;