rs11079738

Variant names:

• chr17-46826683-A-G
• rs11079738
• ENST00000706495.1:c.-116+4765T>C

Variant summary

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

The ENST00000573788.5(WNT3):​n.385+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 ENST00000573788.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 13 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=-0.95).
• 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 rank	MANE	Protein	UniProt
LRRC37A2	XM_024450773.2	c.4810-222373A>G		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000706495.1	c.-116+4765T>C		intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5	n.385+4765T>C		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.142 AC: 5870 AN: 41478

American (AMR) AF: 0.476 AC: 7285 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3468

East Asian (EAS) AF: 0.692 AC: 3582 AN: 5176

South Asian (SAS) AF: 0.669 AC: 3224 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4507 AN: 10502

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

European-Non Finnish (NFE) AF: 0.469 AC: 31886 AN: 67964

Other (OTH) AF: 0.391 AC: 827 AN: 2114

Alfa AF: 0.448 Hom.: 15827

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
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs11079738; hg19: chr17-44904049;