rs1051886

chr12-48966206-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003394.4(WNT10B):c.1059C>T(p.His353=) variant causes a synonymous change. The variant allele was found at a frequency of 0.37 in 1,613,570 control chromosomes in the GnomAD database, including 115,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9136 hom., cov: 33)
  • Exomes 𝑓: 0.37 (106074 hom.)
• Consequence: WNT10B NM_003394.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 5.64

Genes affected

WNT10B (HGNC:12775): (Wnt family member 10B) 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 may be involved in breast cancer, and its protein signaling is likely a molecular switch that governs adipogenesis. This protein is 96% identical to the mouse Wnt10b protein at the amino acid level. This gene is clustered with another family member, WNT1, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 12-48966206-G-A is Benign according to our data. Variant chr12-48966206-G-A is described in ClinVar as [Benign]. Clinvar id is 1175136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-48966206-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT10B	NM_003394.4	c.1059C>T	p.His353=	synonymous_variant	5/5	ENST00000301061.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT10B	ENST00000301061.9	c.1059C>T	p.His353=	synonymous_variant	5/5	1	NM_003394.4	P1
WNT10B	ENST00000403957.5	c.*341C>T		3_prime_UTR_variant	6/6	5
WNT10B	ENST00000407467.5	c.*341C>T		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49537 AN: 152070 Hom.: 9126 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.357

GnomAD3 exomes AF: 0.382 AC: 95727 AN: 250614 Hom.: 19907 AF XY: 0.373 AC XY: 50601 AN XY: 135536

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.375 AC: 547613 AN: 1461380 Hom.: 106074 Cov.: 70 AF XY: 0.371 AC XY: 269867 AN XY: 726966

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.326 AC: 49558 AN: 152190 Hom.: 9136 Cov.: 33 AF XY: 0.329 AC XY: 24500 AN XY: 74412

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.360

Alfa AF: 0.379 Hom.: 14960

Bravo AF: 0.336

Asia WGS AF: 0.363 AC: 1261 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.393

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2018	This variant is associated with the following publications: (PMID: 19702932, 23104151, 29620206) -

Split hand-foot malformation 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Tooth agenesis, selective, 8 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	-0.47
Cadd	Benign	6.6
Dann	Benign	0.62

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: rs1051886; hg19: chr12-49359989; COSMIC: COSV56405412; COSMIC: COSV56405412;