dbSNP rs7207916: WNT3:c.80+16534C>T (chr17-46801984-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.80+16534C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,126 control chromosomes in the GnomAD database, including 8,068 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 0.29 ( 8068 hom., cov: 33)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.532

Publications

13 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.80+16534C>T		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4810-247072G>A		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+16534C>T	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5	P56703
WNT3	ENST00000706495.1 link	c.-115-28075C>T	intron_variant	Intron 2 of 5			ENSP00000516418.1	A0A9L9PXJ3
WNT3	ENST00000573788.5 link	n.491+19124C>T	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44789

AN:

152008

Hom.:

8065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.311

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

GnomAD4 genome

AF:

0.294

AC:

44792

AN:

152126

Hom.:

8068

Cov.:

AF XY:

0.293

AC XY:

21787

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0746

AC:

3100

AN:

41530

American (AMR)

AF:

0.278

AC:

4246

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1245

AN:

3470

East Asian (EAS)

AF:

0.329

AC:

1701

AN:

5178

South Asian (SAS)

AF:

0.294

AC:

1417

AN:

4822

European-Finnish (FIN)

AF:

0.403

AC:

4250

AN:

10546

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27718

AN:

67990

Other (OTH)

AF:

0.311

AC:

654

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1535

3070

4606

6141

7676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.366

Hom.:

8246

Bravo

AF:

0.281

Asia WGS

AF:

0.254

AC:

887

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.64

PhyloP100

0.53

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