17-46791697-G-A

Variant names:

• chr17-46791697-G-A
• rs199494
• NM_030753.5:c.81-17788C>T

Variant summary

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

The NM_030753.5(WNT3):​c.81-17788C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,148 control chromosomes in the GnomAD database, including 20,302 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 0.51 (20302 hom., cov: 33)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 14 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 (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030753.5. 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
	WNT3	NM_030753.5	MANE Select	c.81-17788C>T		intron	N/A	NP_110380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	ENST00000225512.6	TSL:1 MANE Select	c.81-17788C>T		intron	N/A	ENSP00000225512.5
	WNT3	ENST00000706495.1		c.-115-17788C>T		intron	N/A	ENSP00000516418.1
	WNT3	ENST00000573788.5	TSL:4	n.492-17788C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78023 AN: 152030 Hom.: 20295 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.513 AC: 78062 AN: 152148 Hom.: 20302 Cov.: 33 AF XY: 0.515 AC XY: 38319 AN XY: 74370

African (AFR) AF: 0.435 AC: 18058 AN: 41488

American (AMR) AF: 0.496 AC: 7590 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2135 AN: 5164

South Asian (SAS) AF: 0.459 AC: 2212 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6364 AN: 10596

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38151 AN: 67992

Other (OTH) AF: 0.515 AC: 1089 AN: 2116

Alfa AF: 0.541 Hom.: 37886

Bravo AF: 0.503

Asia WGS AF: 0.378 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.71
PhyloP100		-0.042
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: rs199494; hg19: chr17-44869063;