dbSNP rs3809857: WNT3:c.323-900C>A (chr17-46770948-G-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.323-900C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,258 control chromosomes in the GnomAD database, including 5,872 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 0.25 ( 5872 hom., cov: 33)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.356

Publications

25 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 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.323-900C>A		intron	N/A	NP_110380.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WNT3	ENST00000225512.6	TSL:1 MANE Select	c.323-900C>A	intron	N/A	ENSP00000225512.5
WNT3	ENST00000867601.1		c.323-900C>A	intron	N/A	ENSP00000537660.1
WNT3	ENST00000931041.1		c.323-900C>A	intron	N/A	ENSP00000601100.1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37721

AN:

152140

Hom.:

5864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0580

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.239

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

GnomAD4 genome

AF:

0.248

AC:

37736

AN:

152258

Hom.:

5872

Cov.:

AF XY:

0.256

AC XY:

19032

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0579

AC:

2406

AN:

41586

American (AMR)

AF:

0.254

AC:

3889

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

754

AN:

3468

East Asian (EAS)

AF:

0.295

AC:

1529

AN:

5176

South Asian (SAS)

AF:

0.236

AC:

1139

AN:

4826

European-Finnish (FIN)

AF:

0.459

AC:

4869

AN:

10606

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22171

AN:

67974

Other (OTH)

AF:

0.245

AC:

518

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1429

2857

4286

5714

7143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.310

Hom.:

4058

Bravo

AF:

0.222

Asia WGS

AF:

0.237

AC:

822

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

(source)

DANN

Benign

0.83

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over