16-78109710-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016373.4(WWOX):c.173-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,570,608 control chromosomes in the GnomAD database, including 186,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14551 hom., cov: 28)
  • Exomes 𝑓: 0.49 (171668 hom.)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-78109710-C-T is Benign according to our data. Variant chr16-78109710-C-T is described in ClinVar as [Benign]. Clinvar id is 1295626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWOX	NM_016373.4	c.173-68C>T		intron_variant		ENST00000566780.6
WWOX	NM_001291997.2	c.-167-68C>T		intron_variant
WWOX	NM_130791.5	c.173-68C>T		intron_variant
WWOX	NR_120436.3	n.412-68C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWOX	ENST00000566780.6	c.173-68C>T		intron_variant		1	NM_016373.4	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63225 AN: 150972 Hom.: 14537 Cov.: 28

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.487 AC: 691229 AN: 1419520 Hom.: 171668 AF XY: 0.490 AC XY: 347020 AN XY: 708732

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.419 AC: 63264 AN: 151088 Hom.: 14551 Cov.: 28 AF XY: 0.423 AC XY: 31215 AN XY: 73748

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.475

Alfa AF: 0.482 Hom.: 36518

Bravo AF: 0.416

Asia WGS AF: 0.618 AC: 2145 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.45
Dann	Benign	0.78

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: rs2287972; hg19: chr16-78143607; COSMIC: COSV63434259;