16-78124682-G-A

Position:

• chr16-78124682-G-A

Variant summary

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

The NM_016373.4(WWOX):​c.409+9528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,088 control chromosomes in the GnomAD database, including 33,750 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 0.67 (33750 hom., cov: 33)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

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 = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.409+9528G>A		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.70+9528G>A		intron_variant
WWOX	NM_130791.5	c.409+9528G>A		intron_variant
WWOX	NR_120436.3	n.648+9528G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.409+9528G>A		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101127 AN: 151970 Hom.: 33708 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.666 AC: 101227 AN: 152088 Hom.: 33750 Cov.: 33 AF XY: 0.663 AC XY: 49296 AN XY: 74354

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.665

Alfa AF: 0.662 Hom.: 12995

Bravo AF: 0.668

Asia WGS AF: 0.635 AC: 2210 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	0.0030
DANN	Benign	0.40

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: rs1079569; hg19: chr16-78158579;