rs3793771

Positions:

• chr10-100463200-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003393.4(WNT8B):​c.32G>C​(p.Cys11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,612,156 control chromosomes in the GnomAD database, including 40,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (3554 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36783 hom.)
• Consequence: WNT8B NM_003393.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00332734).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT8B	NM_003393.4	c.32G>C	p.Cys11Ser	missense_variant	1/6	ENST00000343737.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT8B	ENST00000343737.6	c.32G>C	p.Cys11Ser	missense_variant	1/6	1	NM_003393.4	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32384 AN: 151952 Hom.: 3535 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.208 AC: 52131 AN: 250590 Hom.: 5744 AF XY: 0.211 AC XY: 28516 AN XY: 135442

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.222 AC: 323800 AN: 1460084 Hom.: 36783 Cov.: 32 AF XY: 0.223 AC XY: 161912 AN XY: 726382

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.213 AC: 32427 AN: 152072 Hom.: 3554 Cov.: 32 AF XY: 0.213 AC XY: 15829 AN XY: 74356

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.204

Alfa AF: 0.224 Hom.: 2924

Bravo AF: 0.211

TwinsUK AF: 0.224 AC: 830

ALSPAC AF: 0.220 AC: 846

ESP6500AA AF: 0.203 AC: 894

ESP6500EA AF: 0.227 AC: 1950

ExAC AF: 0.212 AC: 25801

Asia WGS AF: 0.193 AC: 671 AN: 3478

EpiCase AF: 0.214

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.64
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.11
Sift	Benign	0.22	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.021
MutPred		0.20		Loss of catalytic residue at L12 (P = 0.0085);
MPC		1.0
ClinPred		0.0046	T
GERP RS		4.7
Varity_R		0.073
gMVP		0.49

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

Other links and lift over

dbSNP: rs3793771; hg19: chr10-102222957; COSMIC: COSV100648937;