Variant rs936393 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012478.4(WBP2):c.168+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,520,920 control chromosomes in the GnomAD database, including 28,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3539 hom., cov: 32)

Exomes 𝑓: 0.19 ( 24513 hom. )

Consequence

WBP2
NM_012478.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.422

Variant links:

Genes affected

WBP2 (HGNC:12738): (WW domain binding protein 2) The globular WW domain is composed of 38 to 40 semiconserved amino acids shared by proteins of diverse functions including structural, regulatory, and signaling proteins. The domain is involved in mediating protein-protein interactions through the binding of polyproline ligands. This gene encodes a WW domain binding protein that is a transcriptional coactivator of estrogen receptor alpha and progesterone receptor. Defects in this gene have been associated with hearing impairment. [provided by RefSeq, Jan 2017]

WBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-75851532-A-G is Benign according to our data. Variant chr17-75851532-A-G is described in ClinVar as [Benign]. Clinvar id is 1268857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
WBP2	NM_012478.4 linkuse as main transcript	c.168+36T>C	intron_variant	ENST00000254806.8	NP_036610.2
WBP2	NM_001330499.2 linkuse as main transcript	c.168+36T>C	intron_variant		NP_001317428.1
WBP2	NM_001348170.1 linkuse as main transcript	c.168+36T>C	intron_variant		NP_001335099.1
WBP2	XM_047435712.1 linkuse as main transcript	c.102+36T>C	intron_variant		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8 linkuse as main transcript	c.168+36T>C		intron_variant		1	NM_012478.4	ENSP00000254806	P4	Q969T9-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31567

AN:

152042

Hom.:

3525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.182

AC:

45594

AN:

251186

Hom.:

4360

AF XY:

0.183

AC XY:

24873

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.288

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.135

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.186

AC:

254409

AN:

1368758

Hom.:

24513

Cov.:

AF XY:

0.187

AC XY:

127812

AN XY:

685292

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.208

AC:

31620

AN:

152162

Hom.:

3539

Cov.:

AF XY:

0.204

AC XY:

15197

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.281

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.200

Hom.:

5485

Bravo

AF:

0.216

Asia WGS

AF:

0.176

AC:

610

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Hearing loss, autosomal recessive 107

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

-0.90

CADD

Benign

0.13

DANN

Benign

0.54

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