rs4653533

Positions:

• chr1-228056092-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT3A	NM_033131.4	c.580-2894C>T		intron_variant		ENST00000284523.2	NP_149122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3A	ENST00000284523.2	c.580-2894C>T		intron_variant		1	NM_033131.4	ENSP00000284523.1

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0848

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0948

Gnomad4 OTH AF: 0.0988

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.13

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: rs4653533; hg19: chr1-228243793; COSMIC: COSV52730021;