NM_030761.5:c.276C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_030761.5(WNT4):c.276C>T(p.Leu92Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,613,726 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L92L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0094 ( 22 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 15 hom. )

Consequence

WNT4
NM_030761.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.914

Publications

3 publications found

Variant links:

Genes affected

WNT4 (HGNC:12783): (Wnt family member 4) 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, and is the first signaling molecule shown to influence the sex-determination cascade. It encodes a protein which shows 98% amino acid identity to the Wnt4 protein of mouse and rat. This gene and a nuclear receptor known to antagonize the testis-determining factor play a concerted role in both the control of female development and the prevention of testes formation. This gene and another two family members, WNT2 and WNT7B, may be associated with abnormal proliferation in breast tissue. Mutations in this gene can result in Rokitansky-Kuster-Hauser syndrome and in SERKAL syndrome. [provided by RefSeq, Jul 2008]

WNT4 Gene-Disease associations (from GenCC):

mullerian aplasia and hyperandrogenism
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
SERKAL syndrome
Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

WNT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-22129653-G-A is Benign according to our data. Variant chr1-22129653-G-A is described in ClinVar as Benign. ClinVar VariationId is 772252.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.914 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0094 (1431/152282) while in subpopulation AFR AF = 0.0324 (1348/41556). AF 95% confidence interval is 0.031. There are 22 homozygotes in GnomAd4. There are 685 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AD,AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT4	NM_030761.5	MANE Select	c.276C>T	p.Leu92Leu	synonymous	Exon 2 of 5	NP_110388.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT4	ENST00000290167.11	TSL:1 MANE Select	c.276C>T	p.Leu92Leu	synonymous	Exon 2 of 5	ENSP00000290167.5	P56705-1
WNT4	ENST00000951124.1		c.276C>T	p.Leu92Leu	synonymous	Exon 2 of 5	ENSP00000621183.1
WNT4	ENST00000901549.1		c.276C>T	p.Leu92Leu	synonymous	Exon 2 of 5	ENSP00000571608.1

Frequencies

GnomAD3 genomes

AF:

0.00938

AC:

1428

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00242

AC:

605

AN:

250172

AF XY:

0.00177

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000948

AC:

1386

AN:

1461444

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

571

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.0345

AC:

1154

AN:

33480

American (AMR)

AF:

0.00136

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.000227

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53006

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1112002

Other (OTH)

AF:

0.00194

AC:

117

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

183

274

366

457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00940

AC:

1431

AN:

152282

Hom.:

Cov.:

AF XY:

0.00920

AC XY:

685

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0324

AC:

1348

AN:

41556

American (AMR)

AF:

0.00385

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.000416

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68024

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00420

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.1

(source)

DANN

Benign

0.70

PhyloP100

0.91

PromoterAI

0.0083

Neutral

(source)

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over