chr16-78115170-A-C

Position:

chr16-78115170-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016373.4(WWOX):c.409+16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,613,652 control chromosomes in the GnomAD database, including 66,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4675 hom., cov: 33)

Exomes 𝑓: 0.29 ( 62023 hom. )

Consequence

WWOX
NM_016373.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0300

Variant links:

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]

WWOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-78115170-A-C is Benign according to our data. Variant chr16-78115170-A-C is described in ClinVar as [Benign]. Clinvar id is 260738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
WWOX	NM_016373.4 link	c.409+16A>C	intron_variant	ENST00000566780.6	NP_057457.1	Q9NZC7-1A0A411HBC7
WWOX	NM_001291997.2 link	c.70+16A>C	intron_variant		NP_001278926.1	Q9NZC7
WWOX	NM_130791.5 link	c.409+16A>C	intron_variant		NP_570607.1	Q9NZC7-3
WWOX	NR_120436.3 link	n.648+16A>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWOX	ENST00000566780.6 link	c.409+16A>C		intron_variant		1	NM_016373.4	ENSP00000457230.1		Q9NZC7-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34230

AN:

152086

Hom.:

4672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.262

AC:

65189

AN:

248674

Hom.:

9310

AF XY:

0.266

AC XY:

35862

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.286

AC:

418320

AN:

1461448

Hom.:

62023

Cov.:

AF XY:

0.285

AC XY:

207177

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0471

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.225

AC:

34225

AN:

152204

Hom.:

4675

Cov.:

AF XY:

0.226

AC XY:

16808

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0566

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.163

Hom.:

386

Bravo

AF:

0.210

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 39. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autosomal recessive spinocerebellar ataxia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.13

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over