Genetic Variant WNT3:c.80+4583G>A (chr17-46813935-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.80+4583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,148 control chromosomes in the GnomAD database, including 16,303 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 0.45 ( 16303 hom., cov: 33)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

11 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.80+4583G>A		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2 link	c.4810-235121C>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.80+4583G>A	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1 link	c.-116+17513G>A	intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5 link	n.491+7173G>A	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68235

AN:

152030

Hom.:

16285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.437

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

GnomAD4 genome

AF:

0.449

AC:

68292

AN:

152148

Hom.:

16303

Cov.:

AF XY:

0.451

AC XY:

33572

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.296

AC:

12271

AN:

41506

American (AMR)

AF:

0.502

AC:

7682

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1855

AN:

3472

East Asian (EAS)

AF:

0.685

AC:

3546

AN:

5176

South Asian (SAS)

AF:

0.673

AC:

3242

AN:

4814

European-Finnish (FIN)

AF:

0.461

AC:

4888

AN:

10592

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33462

AN:

67984

Other (OTH)

AF:

0.443

AC:

936

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1867

3735

5602

7470

9337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.487

Hom.:

65572

Bravo

AF:

0.447

Asia WGS

AF:

0.667

AC:

2317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.15

(source)

DANN

Benign

0.34

PhyloP100

-1.7

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