Variant 10-100482762-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003393.4(WNT8B):c.1002C>A(p.Ser334Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,592,354 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 7 hom. )

Consequence

WNT8B
NM_003393.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.575

Variant links:

Genes affected

WNT8B (HGNC:12789): (Wnt family member 8B) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 95%, 86% and 71% amino acid identity to the mouse, zebrafish and Xenopus Wnt8B proteins, respectively. The expression patterns of the human and mouse genes appear identical and are restricted to the developing brain. The chromosomal location of this gene to 10q24 suggests it as a candidate gene for partial epilepsy. [provided by RefSeq, Jul 2008]

WNT8B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008397996).

BP6

Variant 10-100482762-C-A is Benign according to our data. Variant chr10-100482762-C-A is described in ClinVar as [Benign]. Clinvar id is 782772.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00704 (1072/152312) while in subpopulation AFR AF= 0.0239 (993/41578). AF 95% confidence interval is 0.0226. There are 9 homozygotes in gnomad4. There are 510 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1072 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT8B	NM_003393.4 linkuse as main transcript	c.1002C>A	p.Ser334Arg	missense_variant	6/6	ENST00000343737.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT8B	ENST00000343737.6 linkuse as main transcript	c.1002C>A	p.Ser334Arg	missense_variant	6/6	1	NM_003393.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00703

AC:

1070

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00185

AC:

406

AN:

219052

Hom.:

AF XY:

0.00153

AC XY:

185

AN XY:

121020

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.00190

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000261

Gnomad OTH exome

AF:

0.000930

GnomAD4 exome

AF:

0.000783

AC:

1128

AN:

1440042

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

473

AN XY:

713164

show subpopulations

Gnomad4 AFR exome

AF:

0.0225

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000475

Gnomad4 FIN exome

AF:

0.0000586

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00704

AC:

1072

AN:

152312

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.000735

Hom.:

Bravo

AF:

0.00787

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0233

AC:

ESP6500EA

AF:

0.000516

AC:

ExAC

AF:

0.00198

AC:

234

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0084

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.74

MutationTaster

Benign

0.88

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.3

REVEL

Benign

0.19

Sift

Benign

0.12

Sift4G

Benign

0.37

Polyphen

0.27

Vest4

0.32

MutPred

0.38

Loss of phosphorylation at S334 (P = 0.0497);

MVP

0.36

MPC

0.95

ClinPred

0.038

GERP RS

2.6

Varity_R

0.12

gMVP

0.64

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