chr16-79080130-G-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_016373.4(WWOX):c.1057-131478G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 152,250 control chromosomes in the GnomAD database, including 49 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 0.025 ( 49 hom., cov: 32)
Consequence
WWOX
NM_016373.4 intron
NM_016373.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.209
Publications
1 publications found
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 Gene-Disease associations (from GenCC):
- genetic developmental and epileptic encephalopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive spinocerebellar ataxia 12Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
- developmental and epileptic encephalopathy, 28Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- 46,XY partial gonadal dysgenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0247 (3758/152250) while in subpopulation AFR AF = 0.0422 (1752/41548). AF 95% confidence interval is 0.0405. There are 49 homozygotes in GnomAd4. There are 1846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 49 AR,AD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.1057-131478G>C | intron_variant | Intron 8 of 8 | ENST00000566780.6 | NP_057457.1 | ||
WWOX | NM_001291997.2 | c.718-131478G>C | intron_variant | Intron 7 of 7 | NP_001278926.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0247 AC: 3755AN: 152132Hom.: 49 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3755
AN:
152132
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0247 AC: 3758AN: 152250Hom.: 49 Cov.: 32 AF XY: 0.0248 AC XY: 1846AN XY: 74448 show subpopulations
GnomAD4 genome
AF:
AC:
3758
AN:
152250
Hom.:
Cov.:
32
AF XY:
AC XY:
1846
AN XY:
74448
show subpopulations
African (AFR)
AF:
AC:
1752
AN:
41548
American (AMR)
AF:
AC:
253
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
54
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
93
AN:
4828
European-Finnish (FIN)
AF:
AC:
254
AN:
10602
Middle Eastern (MID)
AF:
AC:
6
AN:
294
European-Non Finnish (NFE)
AF:
AC:
1299
AN:
68022
Other (OTH)
AF:
AC:
45
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
186
372
558
744
930
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
42
84
126
168
210
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
56
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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