rs12917833

chr16-78118704-C-Gchr16-78118704-C-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+3550C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,126 control chromosomes in the GnomAD database, including 1,721 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 0.14 (1721 hom., cov: 31)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.409+3550C>G		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.70+3550C>G		intron_variant
WWOX	NM_130791.5	c.409+3550C>G		intron_variant
WWOX	NR_120436.3	n.648+3550C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.409+3550C>G		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21119 AN: 152008 Hom.: 1721 Cov.: 31

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.139 AC: 21116 AN: 152126 Hom.: 1721 Cov.: 31 AF XY: 0.140 AC XY: 10396 AN XY: 74354

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0879 Hom.: 136

Bravo AF: 0.130

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.32
Dann	Benign	0.42

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: rs12917833; hg19: chr16-78152601;