Genetic Variant WNT3:c.80+17616A>G (chr17-46800902-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030753.5(WNT3):c.80+17616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,146 control chromosomes in the GnomAD database, including 54,539 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 0.84 ( 54539 hom., cov: 31)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Publications

7 publications found

Variant links:

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]

WNT3 links:

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]

LRRC37A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.80+17616A>G		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4810-248154T>C		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT3	ENST00000225512.6 link	c.80+17616A>G	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5	P56703
WNT3	ENST00000706495.1 link	c.-115-26993A>G	intron_variant	Intron 2 of 5			ENSP00000516418.1	A0A9L9PXJ3
WNT3	ENST00000573788.5 link	n.491+20206A>G	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

128147

AN:

152028

Hom.:

54502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.720

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.921

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.892

Gnomad OTH

AF:

0.858

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

GnomAD4 genome

AF:

0.843

AC:

128245

AN:

152146

Hom.:

54539

Cov.:

AF XY:

0.843

AC XY:

62747

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.720

AC:

29866

AN:

41472

American (AMR)

AF:

0.856

AC:

13073

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3157

AN:

3470

East Asian (EAS)

AF:

0.939

AC:

4859

AN:

5174

South Asian (SAS)

AF:

0.921

AC:

4447

AN:

4826

European-Finnish (FIN)

AF:

0.876

AC:

9285

AN:

10596

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.892

AC:

60678

AN:

68006

Other (OTH)

AF:

0.860

AC:

1819

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

971

1943

2914

3886

4857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.878

Hom.:

90402

Bravo

AF:

0.837

Asia WGS

AF:

0.930

AC:

3236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.045

(source)

DANN

Benign

0.32

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over