17-46829583-T-C

Variant names:

• chr17-46829583-T-C
• rs8069437
• ENST00000706495.1:c.-116+1865A>G

Variant summary

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

The ENST00000706495.1(WNT3):​c.-116+1865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,012 control chromosomes in the GnomAD database, including 51,539 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 0.82 (51539 hom., cov: 31)
• Consequence: WNT3 ENST00000706495.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 20 publications found

Genes affected

WNT3 (HGNC:12782): (Wnt family member 3) 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 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region. [provided by RefSeq, Jul 2008]

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706495.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	ENST00000706495.1		c.-116+1865A>G		intron	N/A	ENSP00000516418.1
	WNT3	ENST00000573788.5	TSL:4	n.385+1865A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124781 AN: 151894 Hom.: 51506 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.821 AC: 124871 AN: 152012 Hom.: 51539 Cov.: 31 AF XY: 0.826 AC XY: 61376 AN XY: 74286

African (AFR) AF: 0.840 AC: 34842 AN: 41488

American (AMR) AF: 0.863 AC: 13186 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2881 AN: 3466

East Asian (EAS) AF: 0.999 AC: 5162 AN: 5168

South Asian (SAS) AF: 0.943 AC: 4547 AN: 4820

European-Finnish (FIN) AF: 0.777 AC: 8210 AN: 10566

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53362 AN: 67900

Other (OTH) AF: 0.837 AC: 1769 AN: 2114

Alfa AF: 0.803 Hom.: 54607

Bravo AF: 0.826

Asia WGS AF: 0.962 AC: 3345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8069437; hg19: chr17-44906949;