dbSNP rs56318008: WNT4:c.-271G>A (chr1-22143914-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000441048.1(WNT4):c.-271G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,258 control chromosomes in the GnomAD database, including 2,203 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 0.14 ( 2202 hom., cov: 32)

Exomes 𝑓: 0.21 ( 1 hom. )

Consequence

WNT4
ENST00000441048.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0380

Publications

27 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
SERKAL syndrome
Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

WNT4 links:

ENSG00000285873 (HGNC:):

ENSG00000285873 links:

Genome browser will be placed here

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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105376845	XR_947050.1 link	n.53+2909C>T	intron_variant	Intron 1 of 4
LOC105376845	XR_947051.3 link	n.142+923C>T	intron_variant	Intron 1 of 4
LOC105376845	XR_947056.2 link	n.142+923C>T	intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
WNT4	ENST00000441048.1 link	c.-271G>A	5_prime_UTR_variant	Exon 1 of 3	5	ENSP00000388925.1	B1AJZ6
ENSG00000285873	ENST00000648968.1 link	n.55+1010C>T	intron_variant	Intron 1 of 4
ENSG00000285873	ENST00000808862.1 link	n.36+1010C>T	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20729

AN:

152082

Hom.:

2200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.0698

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.207

AC:

AN:

Hom.:

Cov.:

AF XY:

0.217

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.188

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.267

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.136

AC:

20738

AN:

152200

Hom.:

2202

Cov.:

AF XY:

0.144

AC XY:

10687

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0316

AC:

1312

AN:

41548

American (AMR)

AF:

0.242

AC:

3700

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0698

AC:

242

AN:

3468

East Asian (EAS)

AF:

0.508

AC:

2621

AN:

5162

South Asian (SAS)

AF:

0.195

AC:

938

AN:

4812

European-Finnish (FIN)

AF:

0.164

AC:

1733

AN:

10598

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9705

AN:

67992

Other (OTH)

AF:

0.125

AC:

264

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

874

1748

2622

3496

4370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.147

Hom.:

816

Bravo

AF:

0.141

Asia WGS

AF:

0.297

AC:

1030

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.0

(source)

DANN

Benign

0.54

PhyloP100

-0.038

PromoterAI

-0.10

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over