chr16-78432807-C-A

Position:

• chr16-78432807-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016373.4(WWOX):​c.1056+55C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,612,774 control chromosomes in the GnomAD database, including 254 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 0.020 (48 hom., cov: 32)
  • Exomes 𝑓: 0.014 (206 hom.)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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]

WWOX (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0201 (3054/152306) while in subpopulation AFR AF= 0.0432 (1796/41560). AF 95% confidence interval is 0.0416. There are 48 homozygotes in gnomad4. There are 1473 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1056+55C>A		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.717+55C>A		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1056+55C>A		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3051 AN: 152188 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0136 AC: 19867 AN: 1460468 Hom.: 206 AF XY: 0.0139 AC XY: 10085 AN XY: 726622

Gnomad4 AFR exome AF: 0.0449

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.0220

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0187

Gnomad4 FIN exome AF: 0.00119

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.0201 AC: 3054 AN: 152306 Hom.: 48 Cov.: 32 AF XY: 0.0198 AC XY: 1473 AN XY: 74482

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.0223

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.64

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: rs11150078; hg19: chr16-78466704;