12-48965910-T-C

Position:

• chr12-48965910-T-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.*185A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 677,174 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (46 hom.)
• Consequence: WNT10B NM_003394.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0990

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=-0.83).
• BP6: Variant 12-48965910-T-C is Benign according to our data. Variant chr12-48965910-T-C is described in ClinVar as [Benign]. Clinvar id is 1225904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT10B	NM_003394.4	c.*185A>G		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.*185A>G		3_prime_UTR_variant	5/5	1	NM_003394.4	ENSP00000301061.4
WNT10B	ENST00000407467.5	c.*637A>G		3_prime_UTR_variant	6/6	2		ENSP00000384691.1
WNT10B	ENST00000403957.5	c.*637A>G		3_prime_UTR_variant	6/6	5		ENSP00000385980.1

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3561 AN: 152038 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0230

GnomAD4 exome AF: 0.00302 AC: 1583 AN: 525018 Hom.: 46 Cov.: 6 AF XY: 0.00249 AC XY: 684 AN XY: 275102

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.0234 AC: 3565 AN: 152156 Hom.: 135 Cov.: 32 AF XY: 0.0213 AC XY: 1586 AN XY: 74390

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0228

Alfa AF: 0.0110 Hom.: 12

Bravo AF: 0.0264

Asia WGS AF: 0.00520 AC: 18 AN: 3478

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	Jun 28, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.84

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: rs77211836; hg19: chr12-49359693;