16-79055972-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016373.4(WWOX):​c.1057-155636T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,050 control chromosomes in the GnomAD database, including 22,244 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 0.54 ( 22244 hom., cov: 32)

Consequence

WWOX
NM_016373.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.845
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WWOXNM_016373.4 linkc.1057-155636T>C intron_variant Intron 8 of 8 ENST00000566780.6 NP_057457.1 Q9NZC7-1A0A411HBC7
WWOXNM_001291997.2 linkc.718-155636T>C intron_variant Intron 7 of 7 NP_001278926.1 Q9NZC7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WWOXENST00000566780.6 linkc.1057-155636T>C intron_variant Intron 8 of 8 1 NM_016373.4 ENSP00000457230.1 Q9NZC7-1

Frequencies

GnomAD3 genomes
AF:
0.537
AC:
81546
AN:
151932
Hom.:
22223
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.521
Gnomad AMI
AF:
0.600
Gnomad AMR
AF:
0.576
Gnomad ASJ
AF:
0.552
Gnomad EAS
AF:
0.308
Gnomad SAS
AF:
0.408
Gnomad FIN
AF:
0.567
Gnomad MID
AF:
0.474
Gnomad NFE
AF:
0.558
Gnomad OTH
AF:
0.524
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.537
AC:
81609
AN:
152050
Hom.:
22244
Cov.:
32
AF XY:
0.534
AC XY:
39725
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.521
Gnomad4 AMR
AF:
0.577
Gnomad4 ASJ
AF:
0.552
Gnomad4 EAS
AF:
0.307
Gnomad4 SAS
AF:
0.407
Gnomad4 FIN
AF:
0.567
Gnomad4 NFE
AF:
0.558
Gnomad4 OTH
AF:
0.520
Alfa
AF:
0.552
Hom.:
21132
Bravo
AF:
0.539
Asia WGS
AF:
0.390
AC:
1354
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs1121404; hg19: chr16-79089869; API