rs11150078

Variant names:

• chr16-78432807-C-A
• rs11150078
• NM_016373.4:c.1056+55C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-78432807-C-A
• chr16-78432807-C-G
• chr16-78432807-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016373.4(WWOX):​c.1056+55C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,612,774 control chromosomes in the GnomAD database, including 254 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 0.020 (48 hom., cov: 32)
  • Exomes 𝑓: 0.014 (206 hom.)
• Consequence: WWOX NM_016373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 5 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 encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive spinocerebellar ataxia 12

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• developmental and epileptic encephalopathy, 28

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0201 (3054/152306) while in subpopulation AFR AF = 0.0432 (1796/41560). AF 95% confidence interval is 0.0416. There are 48 homozygotes in GnomAd4. There are 1473 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 48 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWOX	NM_016373.4	MANE Select	c.1056+55C>A		intron	N/A	NP_057457.1
	WWOX	NM_001291997.2		c.717+55C>A		intron	N/A	NP_001278926.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWOX	ENST00000566780.6	TSL:1 MANE Select	c.1056+55C>A		intron	N/A	ENSP00000457230.1
	WWOX	ENST00000408984.7	TSL:1	c.1056+55C>A		intron	N/A	ENSP00000386161.3
	WWOX	ENST00000402655.6	TSL:1	c.409+317653C>A		intron	N/A	ENSP00000384238.2

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3051 AN: 152188 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0136 AC: 19867 AN: 1460468 Hom.: 206 AF XY: 0.0139 AC XY: 10085 AN XY: 726622

African (AFR) AF: 0.0449 AC: 1501 AN: 33448

American (AMR) AF: 0.0123 AC: 549 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0220 AC: 574 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0187 AC: 1606 AN: 86072

European-Finnish (FIN) AF: 0.00119 AC: 63 AN: 53102

Middle Eastern (MID) AF: 0.0350 AC: 196 AN: 5598

European-Non Finnish (NFE) AF: 0.0130 AC: 14415 AN: 1111370

Other (OTH) AF: 0.0159 AC: 962 AN: 60342

GnomAD4 genome AF: 0.0201 AC: 3054 AN: 152306 Hom.: 48 Cov.: 32 AF XY: 0.0198 AC XY: 1473 AN XY: 74482

African (AFR) AF: 0.0432 AC: 1796 AN: 41560

American (AMR) AF: 0.0146 AC: 223 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4820

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10628

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 840 AN: 68034

Other (OTH) AF: 0.0217 AC: 46 AN: 2116

Alfa AF: 0.0138 Hom.: 18

Bravo AF: 0.0223

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.64
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11150078; hg19: chr16-78466704;