rs12447067

Positions:

• chr16-78961577-T-C
• chr16-78961577-T-G

Variant summary

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

The NM_016373.4(WWOX):​c.1057-250031T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,728 control chromosomes in the GnomAD database, including 8,316 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 0.31 (8316 hom., cov: 30)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-250031T>C		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-250031T>C		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-250031T>C		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46943 AN: 151610 Hom.: 8291 Cov.: 30

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.310 AC: 47006 AN: 151728 Hom.: 8316 Cov.: 30 AF XY: 0.302 AC XY: 22419 AN XY: 74128

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.320

Alfa AF: 0.224 Hom.: 2146

Bravo AF: 0.334

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs12447067; hg19: chr16-78995474;