chr17-46768172-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030753.5(WNT3):c.*8+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,246,776 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 20 hom., cov: 32)

Exomes 𝑓: 0.017 ( 238 hom. )

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.606

Publications

2 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:

Genome browser will be placed here

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=-0.66).

BP6

Variant 17-46768172-C-T is Benign according to our data. Variant chr17-46768172-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.014 (2140/152316) while in subpopulation NFE AF = 0.0214 (1457/68032). AF 95% confidence interval is 0.0205. There are 20 homozygotes in GnomAd4. There are 1015 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.*8+140G>A		intron_variant	Intron 4 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4809+217653C>T		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+140G>A		intron_variant	Intron 4 of 4	1	NM_030753.5	ENSP00000225512.5		P56703

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2140

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00398

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.0173

AC:

18967

AN:

1094460

Hom.:

238

AF XY:

0.0171

AC XY:

9352

AN XY:

547720

show subpopulations

African (AFR)

AF:

0.00274

AC:

AN:

25586

American (AMR)

AF:

0.00277

AC:

AN:

31760

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

21380

East Asian (EAS)

AF:

0.00

AC:

AN:

34300

South Asian (SAS)

AF:

0.00204

AC:

140

AN:

68714

European-Finnish (FIN)

AF:

0.0365

AC:

1254

AN:

34354

Middle Eastern (MID)

AF:

0.00263

AC:

AN:

3424

European-Non Finnish (NFE)

AF:

0.0202

AC:

16674

AN:

827112

Other (OTH)

AF:

0.0138

AC:

658

AN:

47830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

965

1930

2895

3860

4825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0140

AC:

2140

AN:

152316

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1015

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00397

AC:

165

AN:

41574

American (AMR)

AF:

0.00464

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00311

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0333

AC:

354

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0214

AC:

1457

AN:

68032

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

205

308

410

513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 16, 2019

GeneDx

Significance:Likely 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

-0.66

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.61

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr17-46768172-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over