dbSNP rs199495: WNT3:c.81-17155C>T (chr17-46791064-G-A) – 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.81-17155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,964 control chromosomes in the GnomAD database, including 8,671 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 0.32 ( 8671 hom., cov: 32)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.428

Publications

6 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.81-17155C>T		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2 link	c.4809+240545G>A		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
WNT3	ENST00000225512.6 link	c.81-17155C>T	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1 link	c.-115-17155C>T	intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5 link	n.492-17155C>T	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48308

AN:

151846

Hom.:

8666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.330

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

GnomAD4 genome

AF:

0.318

AC:

48322

AN:

151964

Hom.:

8671

Cov.:

AF XY:

0.317

AC XY:

23537

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.138

AC:

5721

AN:

41442

American (AMR)

AF:

0.290

AC:

4432

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1255

AN:

3472

East Asian (EAS)

AF:

0.332

AC:

1713

AN:

5154

South Asian (SAS)

AF:

0.304

AC:

1463

AN:

4810

European-Finnish (FIN)

AF:

0.410

AC:

4324

AN:

10550

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28251

AN:

67950

Other (OTH)

AF:

0.328

AC:

693

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1538

3075

4613

6150

7688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.381

Hom.:

7061

Bravo

AF:

0.306

Asia WGS

AF:

0.260

AC:

905

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.34

(source)

DANN

Benign

0.63

PhyloP100

-0.43

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