Variant chr2-74459692-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012477.4(WBP1):c.119G>A(p.Ser40Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 1,614,004 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 1 hom. )

Consequence

WBP1
NM_012477.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

WBP1 (HGNC:12737): (WW domain binding protein 1) The globular WW domain, named for the conserved tryptophan residues in the protein motif present in various structural and regulatory proteins, is known to play a role in the mediation of protein-protein interactions. This gene encodes a ligand of the WW domain of the Yes kinase-associated protein. Readthrough transcription of the neighboring upstream gene, which encodes INO80 complex subunit B, into this gene generates a non-coding transcript. [provided by RefSeq, Feb 2011]

WBP1 links:

INO80B-WBP1 (HGNC:):

INO80B-WBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10816395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WBP1	NM_012477.4 linkuse as main transcript	c.119G>A	p.Ser40Asn	missense_variant	2/4	ENST00000233615.7
INO80B-WBP1	NR_037849.1 linkuse as main transcript	n.1211G>A		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP1	ENST00000233615.7 linkuse as main transcript	c.119G>A	p.Ser40Asn	missense_variant	2/4	1	NM_012477.4	P4

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000318

AC:

AN:

251444

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000615

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000775

AC:

1133

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000733

AC XY:

533

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000948

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.000565

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000474

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.119G>A (p.S40N) alteration is located in exon 2 (coding exon 2) of the WBP1 gene. This alteration results from a G to A substitution at nucleotide position 119, causing the serine (S) at amino acid position 40 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;.;T;T

Eigen

Benign

0.093

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.016

D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;T

Polyphen

0.72

P;.;P;.

Vest4

0.27

MVP

0.36

MPC

0.093

ClinPred

0.17

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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