rs2270031

Positions:

• chr12-1633343-C-G

Variant summary

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

The NM_032642.3(WNT5B):​c.328+438C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 152,250 control chromosomes in the GnomAD database, including 723 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 0.074 (723 hom., cov: 32)
• Consequence: WNT5B NM_032642.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

Genes affected

WNT5B (HGNC:16265): (Wnt family member 5B) 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 encodes a protein which shows 94% and 80% amino acid identity to the mouse Wnt5b protein and the human WNT5A protein, respectively. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5B	NM_032642.3	c.328+438C>G		intron_variant		ENST00000397196.7	NP_116031.1
WNT5B	NM_030775.2	c.328+438C>G		intron_variant			NP_110402.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT5B	ENST00000397196.7	c.328+438C>G		intron_variant		1	NM_032642.3	ENSP00000380379.2

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11289 AN: 152132 Hom.: 716 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0659

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0743 AC: 11317 AN: 152250 Hom.: 723 Cov.: 32 AF XY: 0.0763 AC XY: 5683 AN XY: 74438

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0669

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.0873

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0533 Hom.: 43

Bravo AF: 0.0784

Asia WGS AF: 0.209 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.51

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: rs2270031; hg19: chr12-1742509;