rs4653533

Variant names:

• chr1-228056092-C-T
• rs4653533
• NM_033131.4:c.580-2894C>T

Variant summary

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

The NM_033131.4(WNT3A):​c.580-2894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,204 control chromosomes in the GnomAD database, including 1,153 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 0.12 (1153 hom., cov: 32)
• Consequence: WNT3A NM_033131.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 4 publications found

Genes affected

WNT3A (HGNC:15983): (Wnt family member 3A) 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 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. This gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033131.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3A	NM_033131.4	MANE Select	c.580-2894C>T		intron	N/A	NP_149122.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3A	ENST00000284523.2	TSL:1 MANE Select	c.580-2894C>T		intron	N/A	ENSP00000284523.1
	WNT3A	ENST00000948304.1		c.580-3011C>T		intron	N/A	ENSP00000618363.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17664 AN: 152086 Hom.: 1152 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.0998

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

GnomAD4 genome AF: 0.116 AC: 17681 AN: 152204 Hom.: 1153 Cov.: 32 AF XY: 0.117 AC XY: 8721 AN XY: 74412

African (AFR) AF: 0.141 AC: 5863 AN: 41524

American (AMR) AF: 0.107 AC: 1631 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1231 AN: 5160

South Asian (SAS) AF: 0.155 AC: 746 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10594

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0948 AC: 6449 AN: 68012

Other (OTH) AF: 0.0988 AC: 209 AN: 2116

Alfa AF: 0.103 Hom.: 173

Bravo AF: 0.119

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.13
PhyloP100		-1.7
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: rs4653533; hg19: chr1-228243793; COSMIC: COSV52730021;