chr17-46782349-T-C

Variant names:

• chr17-46782349-T-C
• rs70602
• NM_030753.5:c.81-8440A>G

Variant summary

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

The NM_030753.5(WNT3):​c.81-8440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,128 control chromosomes in the GnomAD database, including 54,514 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 0.84 (54514 hom., cov: 31)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 23 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5	c.81-8440A>G		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+231830T>C		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6	c.81-8440A>G		intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1	c.-115-8440A>G		intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5	n.492-8440A>G		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128291 AN: 152010 Hom.: 54449 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.844 AC: 128416 AN: 152128 Hom.: 54514 Cov.: 31 AF XY: 0.853 AC XY: 63450 AN XY: 74370

African (AFR) AF: 0.891 AC: 36958 AN: 41490

American (AMR) AF: 0.824 AC: 12603 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2605 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5149 AN: 5154

South Asian (SAS) AF: 0.941 AC: 4528 AN: 4814

European-Finnish (FIN) AF: 0.928 AC: 9841 AN: 10608

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54102 AN: 67978

Other (OTH) AF: 0.817 AC: 1728 AN: 2114

Alfa AF: 0.832 Hom.: 6573

Bravo AF: 0.835

Asia WGS AF: 0.969 AC: 3371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs70602; hg19: chr17-44859715;