rs11079738

Positions:

• chr17-46826683-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000706495.1(WNT3):​c.-116+4765T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,020 control chromosomes in the GnomAD database, including 13,758 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 0.39 (13758 hom., cov: 32)
• Consequence: WNT3 ENST00000706495.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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]

WNT3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC37A2	XM_024450773.2	c.4810-222373A>G		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000706495.1	c.-116+4765T>C		intron_variant				ENSP00000516418.1
WNT3	ENST00000573788.5	n.385+4765T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59322 AN: 151904 Hom.: 13751 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.390 AC: 59333 AN: 152020 Hom.: 13758 Cov.: 32 AF XY: 0.394 AC XY: 29298 AN XY: 74290

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.391

Alfa AF: 0.463 Hom.: 10613

Bravo AF: 0.384

Asia WGS AF: 0.652 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.017
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11079738; hg19: chr17-44904049;