Genetic Variant WNT3:c.*8+232T>C (chr17-46768080-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030753.5(WNT3):c.*8+232T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,280 control chromosomes in the GnomAD database, including 67,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 67189 hom., cov: 34)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.15

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 17-46768080-A-G is Benign according to our data. Variant chr17-46768080-A-G is described in ClinVar as [Benign]. Clinvar id is 1296567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.*8+232T>C		intron_variant	Intron 4 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4809+217561A>G		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6 link	c.*8+232T>C		intron_variant	Intron 4 of 4	1	NM_030753.5	ENSP00000225512.5		P56703

Frequencies

GnomAD3 genomes

AF:

0.934

AC:

142185

AN:

152162

Hom.:

67148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.969

Gnomad ASJ

AF:

0.979

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.950

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

GnomAD4 genome

AF:

0.934

AC:

142282

AN:

152280

Hom.:

67189

Cov.:

AF XY:

0.936

AC XY:

69711

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.779

AC:

32342

AN:

41516

American (AMR)

AF:

0.969

AC:

14838

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

3394

AN:

3468

East Asian (EAS)

AF:

1.00

AC:

5174

AN:

5174

South Asian (SAS)

AF:

0.999

AC:

4825

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.998

AC:

67883

AN:

68038

Other (OTH)

AF:

0.951

AC:

2012

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

410

820

1229

1639

2049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.960

Hom.:

8758

Bravo

AF:

0.924

Asia WGS

AF:

0.989

AC:

3440

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.22

(source)

DANN

Benign

0.12

PhyloP100

-1.2

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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17-46768080-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over