rs3793771

Variant names:

• chr10-100463200-G-C
• rs3793771
• NM_003393.4:c.32G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-100463200-G-C
• chr10-100463200-G-T

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WNT8B	NM_003393.4	c.32G>C	p.Cys11Ser	missense_variant	Exon 1 of 6	ENST00000343737.6	NP_003384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT8B	ENST00000343737.6	c.32G>C	p.Cys11Ser	missense_variant	Exon 1 of 6	1	NM_003393.4	ENSP00000340677.5

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

GnomAD2 exomes AF: 0.208 AC: 52131 AN: 250590 AF XY: 0.211

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 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

African (AFR) AF: 0.206 AC: 6881 AN: 33406

American (AMR) AF: 0.160 AC: 7120 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5407 AN: 26104

East Asian (EAS) AF: 0.156 AC: 6197 AN: 39662

South Asian (SAS) AF: 0.231 AC: 19900 AN: 86072

European-Finnish (FIN) AF: 0.234 AC: 12500 AN: 53364

Middle Eastern (MID) AF: 0.213 AC: 1227 AN: 5752

European-Non Finnish (NFE) AF: 0.226 AC: 251342 AN: 1110764

Other (OTH) AF: 0.219 AC: 13226 AN: 60330

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

African (AFR) AF: 0.210 AC: 8708 AN: 41452

American (AMR) AF: 0.182 AC: 2778 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3472

East Asian (EAS) AF: 0.130 AC: 674 AN: 5178

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2359 AN: 10580

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15406 AN: 67984

Other (OTH) AF: 0.204 AC: 430 AN: 2112

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
PhyloP100		1.7
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
PromoterAI		0.0070	Neutral
Varity_R		0.073
gMVP		0.49
Mutation Taster		=99/1	polymorphism (auto)

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