12-48970608-G-A

Variant names:

• chr12-48970608-G-A
• rs833843
• NM_003394.4:c.-40-39C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• split hand-foot malformation 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• tooth agenesis, selective, 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003394.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT10B	NM_003394.4	MANE Select	c.-40-39C>T		intron	N/A	NP_003385.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT10B	ENST00000301061.9	TSL:1 MANE Select	c.-40-39C>T		intron	N/A	ENSP00000301061.4
	WNT10B	ENST00000475740.1	TSL:2	n.45C>T		non_coding_transcript_exon	Exon 1 of 2
	WNT10B	ENST00000413630.1	TSL:5	c.-79C>T		5_prime_UTR	Exon 1 of 4	ENSP00000398473.1

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

African (AFR) AF: 0.163 AC: 5009 AN: 30734

American (AMR) AF: 0.347 AC: 12280 AN: 35394

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 10741 AN: 24818

East Asian (EAS) AF: 0.546 AC: 19372 AN: 35508

South Asian (SAS) AF: 0.497 AC: 38892 AN: 78216

European-Finnish (FIN) AF: 0.465 AC: 22281 AN: 47902

Middle Eastern (MID) AF: 0.377 AC: 1786 AN: 4734

European-Non Finnish (NFE) AF: 0.458 AC: 476622 AN: 1040302

Other (OTH) AF: 0.441 AC: 24829 AN: 56332

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

African (AFR) AF: 0.180 AC: 7452 AN: 41504

American (AMR) AF: 0.348 AC: 5329 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2776 AN: 5154

South Asian (SAS) AF: 0.507 AC: 2439 AN: 4810

European-Finnish (FIN) AF: 0.471 AC: 4988 AN: 10600

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31272 AN: 67948

Other (OTH) AF: 0.368 AC: 777 AN: 2114

Alfa AF: 0.421 Hom.: 39022

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		-0.32
PromoterAI		-0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs833843; hg19: chr12-49364391;