chr16-78955452-A-G

Position:

• chr16-78955452-A-G

Variant summary

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

The NM_016373.4(WWOX):​c.1057-256156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,084 control chromosomes in the GnomAD database, including 1,486 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 0.12 (1486 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.1057-256156A>G		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.718-256156A>G		intron_variant			NP_001278926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.1057-256156A>G		intron_variant		1	NM_016373.4	ENSP00000457230.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18410 AN: 151966 Hom.: 1479 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.0926

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.121 AC: 18437 AN: 152084 Hom.: 1486 Cov.: 32 AF XY: 0.117 AC XY: 8704 AN XY: 74330

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.0828

Gnomad4 ASJ AF: 0.0926

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0674 Hom.: 101

Bravo AF: 0.128

Asia WGS AF: 0.0430 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.73

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: rs16949032; hg19: chr16-78989349;