chr16-79025229-C-G

Position:

• chr16-79025229-C-G

Variant summary

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

The NM_016373.4(WWOX):​c.1057-186379C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,154 control chromosomes in the GnomAD database, including 1,845 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 0.15 (1845 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-186379C>G		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-186379C>G		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-186379C>G		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22417 AN: 152036 Hom.: 1844 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.147 AC: 22438 AN: 152154 Hom.: 1845 Cov.: 32 AF XY: 0.147 AC XY: 10941 AN XY: 74364

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.149

Alfa AF: 0.131 Hom.: 185

Bravo AF: 0.160

Asia WGS AF: 0.228 AC: 790 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	0.12
DANN	Benign	0.51

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: rs905781; hg19: chr16-79059126;