rs111769

Variant names:

• chr17-46794621-C-T
• rs111769
• NM_030753.5:c.81-20712G>A

Variant summary

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

The NM_030753.5(WNT3):​c.81-20712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,988 control chromosomes in the GnomAD database, including 9,255 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 0.34 (9255 hom., cov: 30)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5	c.81-20712G>A		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+244102C>T		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.81-20712G>A		intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1	c.-115-20712G>A		intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5	n.492-20712G>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51605 AN: 151870 Hom.: 9250 Cov.: 30

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.340 AC: 51631 AN: 151988 Hom.: 9255 Cov.: 30 AF XY: 0.337 AC XY: 25065 AN XY: 74288

African (AFR) AF: 0.211 AC: 8744 AN: 41480

American (AMR) AF: 0.307 AC: 4687 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3464

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1419 AN: 4808

European-Finnish (FIN) AF: 0.403 AC: 4250 AN: 10550

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28353 AN: 67926

Other (OTH) AF: 0.346 AC: 729 AN: 2108

Alfa AF: 0.394 Hom.: 38324

Bravo AF: 0.333

Asia WGS AF: 0.261 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.67
PhyloP100		-0.19
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: rs111769; hg19: chr17-44871987;