Genetic Variant WNT3:c.81-7869G>A (chr17-46781778-C-T) – 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.81-7869G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,750 control chromosomes in the GnomAD database, including 53,988 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 ( 53988 hom., cov: 31)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.441

Publications

62 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.81-7869G>A		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2 link	c.4809+231259C>T		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
WNT3	ENST00000225512.6 link	c.81-7869G>A	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1 link	c.-115-7869G>A	intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5 link	n.492-7869G>A	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.841

AC:

127517

AN:

151632

Hom.:

53925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.822

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.940

Gnomad FIN

AF:

0.927

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.795

Gnomad OTH

AF:

0.813

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

GnomAD4 genome

AF:

0.841

AC:

127642

AN:

151750

Hom.:

53988

Cov.:

AF XY:

0.850

AC XY:

63030

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.883

AC:

36497

AN:

41350

American (AMR)

AF:

0.823

AC:

12561

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

2598

AN:

3464

East Asian (EAS)

AF:

0.999

AC:

5171

AN:

5176

South Asian (SAS)

AF:

0.941

AC:

4528

AN:

4814

European-Finnish (FIN)

AF:

0.927

AC:

9798

AN:

10568

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.795

AC:

53882

AN:

67814

Other (OTH)

AF:

0.815

AC:

1720

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1021

2042

3064

4085

5106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.808

Hom.:

124608

Bravo

AF:

0.833

Asia WGS

AF:

0.969

AC:

3368

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.59

PhyloP100

-0.44

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