17-46788073-T-G

Variant names:

• chr17-46788073-T-G
• rs2074404
• NM_030753.5:c.81-14164A>C

Variant summary

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

The NM_030753.5(WNT3):​c.81-14164A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,414 control chromosomes in the GnomAD database, including 6,098 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 0.27 (6098 hom., cov: 31)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 56 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	NM_030753.5	MANE Select	c.81-14164A>C		intron	N/A	NP_110380.1	P56703

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	ENST00000225512.6	TSL:1 MANE Select	c.81-14164A>C		intron	N/A	ENSP00000225512.5	P56703
	WNT3	ENST00000867601.1		c.81-14164A>C		intron	N/A	ENSP00000537660.1
	WNT3	ENST00000931041.1		c.81-14164A>C		intron	N/A	ENSP00000601100.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41500 AN: 151310 Hom.: 6096 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.274 AC: 41528 AN: 151414 Hom.: 6098 Cov.: 31 AF XY: 0.271 AC XY: 20028 AN XY: 73960

African (AFR) AF: 0.262 AC: 10800 AN: 41252

American (AMR) AF: 0.401 AC: 6105 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3466

East Asian (EAS) AF: 0.521 AC: 2681 AN: 5142

South Asian (SAS) AF: 0.184 AC: 881 AN: 4780

European-Finnish (FIN) AF: 0.170 AC: 1771 AN: 10428

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16965 AN: 67814

Other (OTH) AF: 0.314 AC: 659 AN: 2102

Alfa AF: 0.266 Hom.: 24870

Bravo AF: 0.297

Asia WGS AF: 0.349 AC: 1213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.41
PhyloP100		-0.34
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: rs2074404; hg19: chr17-44865439;