rs833843

Positions:

• chr12-48970608-G-A
• chr12-48970608-G-C

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.-40-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,506,044 control chromosomes in the GnomAD database, including 152,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11967 hom., cov: 32)
  • Exomes 𝑓: 0.45 (140851 hom.)
• Consequence: WNT10B NM_003394.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.316

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]

WNT10B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-48970608-G-A is Benign according to our data. Variant chr12-48970608-G-A is described in ClinVar as [Benign]. Clinvar id is 1279755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT10B	NM_003394.4	c.-40-39C>T		intron_variant		ENST00000301061.9	NP_003385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT10B	ENST00000301061.9	c.-40-39C>T		intron_variant		1	NM_003394.4	ENSP00000301061.4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57038 AN: 151984 Hom.: 11971 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.452 AC: 611812 AN: 1353940 Hom.: 140851 Cov.: 23 AF XY: 0.454 AC XY: 303721 AN XY: 669644

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.375 AC: 57035 AN: 152104 Hom.: 11967 Cov.: 32 AF XY: 0.377 AC XY: 27997 AN XY: 74348

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.368

Alfa AF: 0.440 Hom.: 24723

Bravo AF: 0.354

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs833843; hg19: chr12-49364391;