rs12828

Positions:

• chr16-79212426-G-A
• chr16-79212426-G-C

Variant summary

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

The NM_016373.4(WWOX):​c.*630G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 314,970 control chromosomes in the GnomAD database, including 46,273 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 0.51 (20925 hom., cov: 33)
  • Exomes 𝑓: 0.54 (25348 hom.)
• Consequence: WWOX NM_016373.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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]

MAF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.*630G>A		3_prime_UTR_variant	9/9	ENST00000566780.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.*630G>A		3_prime_UTR_variant	9/9	1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76733 AN: 151880 Hom.: 20915 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.543 AC: 88516 AN: 162974 Hom.: 25348 Cov.: 3 AF XY: 0.542 AC XY: 44594 AN XY: 82272

Gnomad4 AFR exome AF: 0.325

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.602

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.505 AC: 76764 AN: 151996 Hom.: 20925 Cov.: 33 AF XY: 0.500 AC XY: 37163 AN XY: 74318

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.502

Alfa AF: 0.551 Hom.: 12039

Bravo AF: 0.486

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.46

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: rs12828; hg19: chr16-79246323;