12-1633343-C-G

Variant names:

• chr12-1633343-C-G
• rs2270031
• NM_032642.3:c.328+438C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030775.2(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_030775.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030775.2. 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
	WNT5B	NM_032642.3	MANE Select	c.328+438C>G		intron	N/A	NP_116031.1
	WNT5B	NM_030775.2		c.328+438C>G		intron	N/A	NP_110402.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5B	ENST00000397196.7	TSL:1 MANE Select	c.328+438C>G		intron	N/A	ENSP00000380379.2
	WNT5B	ENST00000310594.7	TSL:1	c.328+438C>G		intron	N/A	ENSP00000308887.3
	WNT5B	ENST00000543071.5	TSL:1	c.328+438C>G		intron	N/A	ENSP00000442348.1

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

African (AFR) AF: 0.141 AC: 5861 AN: 41510

American (AMR) AF: 0.0669 AC: 1024 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1441 AN: 5176

South Asian (SAS) AF: 0.0873 AC: 421 AN: 4822

European-Finnish (FIN) AF: 0.0381 AC: 405 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1938 AN: 68028

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.51
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270031; hg19: chr12-1742509;