rs2548879

chr16-78608909-C-Achr16-78608909-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.1056+176157C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,974 control chromosomes in the GnomAD database, including 17,516 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 0.45 (17516 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.1056+176157C>A		intron_variant		ENST00000566780.6
LOC105371354	XR_001752380.2	n.99+334C>A		intron_variant, non_coding_transcript_variant
WWOX	NM_001291997.2	c.717+176157C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+176157C>A		intron_variant		1	NM_016373.4	P1
	ENST00000684867.1	n.88+334C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68014 AN: 151858 Hom.: 17510 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.448 AC: 68037 AN: 151974 Hom.: 17516 Cov.: 32 AF XY: 0.449 AC XY: 33329 AN XY: 74260

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.497

Alfa AF: 0.485 Hom.: 5339

Bravo AF: 0.446

Asia WGS AF: 0.463 AC: 1609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	3.2
Dann	Benign	0.59

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: rs2548879; hg19: chr16-78642806;