Genetic Variant WNT3:c.81-14164A>C (chr17-46788073-T-G) – 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.81-14164A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,414 control chromosomes in the GnomAD database, including 6,098 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 0.27 ( 6098 hom., cov: 31)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

56 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	NM_030753.5	MANE Select	c.81-14164A>C		intron	N/A	NP_110380.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WNT3	ENST00000225512.6	TSL:1 MANE Select	c.81-14164A>C	intron	N/A	ENSP00000225512.5
WNT3	ENST00000706495.1		c.-115-14164A>C	intron	N/A	ENSP00000516418.1
WNT3	ENST00000573788.5	TSL:4	n.492-14164A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41500

AN:

151310

Hom.:

6096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.315

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

GnomAD4 genome

AF:

0.274

AC:

41528

AN:

151414

Hom.:

6098

Cov.:

AF XY:

0.271

AC XY:

20028

AN XY:

73960

show subpopulations

African (AFR)

AF:

0.262

AC:

10800

AN:

41252

American (AMR)

AF:

0.401

AC:

6105

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1308

AN:

3466

East Asian (EAS)

AF:

0.521

AC:

2681

AN:

5142

South Asian (SAS)

AF:

0.184

AC:

881

AN:

4780

European-Finnish (FIN)

AF:

0.170

AC:

1771

AN:

10428

Middle Eastern (MID)

AF:

0.325

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.250

AC:

16965

AN:

67814

Other (OTH)

AF:

0.314

AC:

659

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1507

3015

4522

6030

7537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.266

Hom.:

24870

Bravo

AF:

0.297

Asia WGS

AF:

0.349

AC:

1213

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.13

(source)

DANN

Benign

0.41

PhyloP100

-0.34

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over