rs12920698

Positions:

• chr16-78124857-G-C
• chr16-78124857-G-T

Variant summary

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

The NM_016373.4(WWOX):​c.409+9703G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,152 control chromosomes in the GnomAD database, including 1,132 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 0.11 (1132 hom., cov: 32)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWOX	NM_016373.4	c.409+9703G>C		intron_variant		ENST00000566780.6	NP_057457.1
WWOX	NM_001291997.2	c.70+9703G>C		intron_variant			NP_001278926.1
WWOX	NM_130791.5	c.409+9703G>C		intron_variant			NP_570607.1
WWOX	NR_120436.3	n.648+9703G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6	c.409+9703G>C		intron_variant		1	NM_016373.4	ENSP00000457230	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16370 AN: 152036 Hom.: 1134 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.108 AC: 16373 AN: 152152 Hom.: 1132 Cov.: 32 AF XY: 0.103 AC XY: 7663 AN XY: 74390

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.0583

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.124

Alfa AF: 0.130 Hom.: 162

Bravo AF: 0.104

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.72

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: rs12920698; hg19: chr16-78158754;