12-48965804-T-G

Position:

• chr12-48965804-T-G

Variant summary

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

The NM_003394.4(WNT10B):​c.*291A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 444,980 control chromosomes in the GnomAD database, including 30,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9140 hom., cov: 32)
  • Exomes 𝑓: 0.37 (21094 hom.)
• Consequence: WNT10B NM_003394.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT10B	NM_003394.4	c.*291A>C		3_prime_UTR_variant	5/5	ENST00000301061.9	NP_003385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT10B	ENST00000301061	c.*291A>C		3_prime_UTR_variant	5/5	1	NM_003394.4	ENSP00000301061.4
WNT10B	ENST00000407467.5	c.*743A>C		3_prime_UTR_variant	6/6	2		ENSP00000384691.1
WNT10B	ENST00000403957.5	c.*743A>C		3_prime_UTR_variant	6/6	5		ENSP00000385980.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49556 AN: 151958 Hom.: 9131 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.367 AC: 107453 AN: 292904 Hom.: 21094 Cov.: 2 AF XY: 0.358 AC XY: 54686 AN XY: 152936

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.326 AC: 49576 AN: 152076 Hom.: 9140 Cov.: 32 AF XY: 0.330 AC XY: 24504 AN XY: 74338

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.360

Alfa AF: 0.374 Hom.: 11902

Bravo AF: 0.337

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.73

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: rs3741627; hg19: chr12-49359587;