rs3790606

Positions:

• chr1-112509564-G-C

Variant summary

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

The NM_024494.3(WNT2B):​c.182+120G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,139,278 control chromosomes in the GnomAD database, including 57,456 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 0.27 (6316 hom., cov: 33)
  • Exomes 𝑓: 0.32 (51140 hom.)
• Consequence: WNT2B NM_024494.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT2B	NM_024494.3	c.182+120G>C		intron_variant		ENST00000369684.5	NP_078613.1
WNT2B	NM_004185.4	c.126-5310G>C		intron_variant			NP_004176.2
WNT2B	NM_001291880.1	c.-94-5310G>C		intron_variant			NP_001278809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT2B	ENST00000369684.5	c.182+120G>C		intron_variant		1	NM_024494.3	ENSP00000358698.4
WNT2B	ENST00000369686.9	c.126-5310G>C		intron_variant		1		ENSP00000358700.4
WNT2B	ENST00000256640.9	c.-94-5310G>C		intron_variant		2		ENSP00000256640.5

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40908 AN: 152068 Hom.: 6316 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.319 AC: 314586 AN: 987092 Hom.: 51140 AF XY: 0.317 AC XY: 155554 AN XY: 491346

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.269 AC: 40906 AN: 152186 Hom.: 6316 Cov.: 33 AF XY: 0.276 AC XY: 20565 AN XY: 74382

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.275

Alfa AF: 0.285 Hom.: 902

Bravo AF: 0.260

Asia WGS AF: 0.318 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.65

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: rs3790606; hg19: chr1-113052186; COSMIC: COSV56673250;