dbSNP rs11650531: WNT3:c.80+21889A>G (chr17-46796629-T-C) – 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+21889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,050 control chromosomes in the GnomAD database, including 3,439 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 0.20 ( 3439 hom., cov: 32)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Publications

10 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 (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.80+21889A>G		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4809+246110T>C		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+21889A>G	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5	P56703
WNT3	ENST00000706495.1 link	c.-115-22720A>G	intron_variant	Intron 2 of 5			ENSP00000516418.1	A0A9L9PXJ3
WNT3	ENST00000573788.5 link	n.492-22720A>G	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30178

AN:

151932

Hom.:

3433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0845

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.200

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

GnomAD4 genome

AF:

0.199

AC:

30191

AN:

152050

Hom.:

3439

Cov.:

AF XY:

0.201

AC XY:

14904

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0843

AC:

3499

AN:

41516

American (AMR)

AF:

0.182

AC:

2788

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

750

AN:

3472

East Asian (EAS)

AF:

0.332

AC:

1712

AN:

5152

South Asian (SAS)

AF:

0.231

AC:

1112

AN:

4806

European-Finnish (FIN)

AF:

0.280

AC:

2951

AN:

10554

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16753

AN:

67944

Other (OTH)

AF:

0.201

AC:

425

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1231

2461

3692

4922

6153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.235

Hom.:

5421

Bravo

AF:

0.191

Asia WGS

AF:

0.235

AC:

817

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

4.6

(source)

DANN

Benign

0.30

PhyloP100

-0.11

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