rs2234593

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_024426.6(WT1):c.1265-32C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 1,603,662 control chromosomes in the GnomAD database, including 8,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1534 hom., cov: 32)

Exomes 𝑓: 0.091 ( 7061 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.270

Publications

11 publications found

Variant links:

COSMIC-nc: COSV60066957

Genes affected

WT1 (HGNC:12796): (WT1 transcription factor) This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]

WT1 Gene-Disease associations (from GenCC):

Denys-Drash syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
Wilms tumor 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Frasier syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WT1 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=-0.82).

BP6

Variant 11-32392787-G-T is Benign according to our data. Variant chr11-32392787-G-T is described in ClinVar as Benign. ClinVar VariationId is 224479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024426.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WT1	NM_024426.6	MANE Select	c.1265-32C>A	intron	N/A	NP_077744.4
WT1	NM_024424.5		c.1265-32C>A	intron	N/A	NP_077742.3	H0Y7K5
WT1	NM_001407044.1		c.1259-32C>A	intron	N/A	NP_001393973.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WT1	ENST00000452863.10	TSL:1 MANE Select	c.1265-32C>A	intron	N/A	ENSP00000415516.5	P19544-7
WT1	ENST00000639563.4	TSL:1	c.1214-32C>A	intron	N/A	ENSP00000492269.3	P19544-8
WT1	ENST00000332351.9	TSL:1	c.1214-32C>A	intron	N/A	ENSP00000331327.5	J3KNN9

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18872

AN:

151990

Hom.:

1531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0905

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0234

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0379

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.0930

AC:

23291

AN:

250436

AF XY:

0.0944

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0555

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0247

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.0903

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0915

AC:

132764

AN:

1451554

Hom.:

7061

Cov.:

AF XY:

0.0921

AC XY:

66545

AN XY:

722396

show subpopulations

African (AFR)

AF:

0.238

AC:

7920

AN:

33282

American (AMR)

AF:

0.0607

AC:

2708

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4036

AN:

26030

East Asian (EAS)

AF:

0.0191

AC:

758

AN:

39604

South Asian (SAS)

AF:

0.120

AC:

10354

AN:

85958

European-Finnish (FIN)

AF:

0.0463

AC:

2460

AN:

53106

Middle Eastern (MID)

AF:

0.151

AC:

866

AN:

5736

European-Non Finnish (NFE)

AF:

0.0884

AC:

97519

AN:

1103236

Other (OTH)

AF:

0.102

AC:

6143

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

6102

12205

18307

24410

30512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3740

7480

11220

14960

18700

<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:

0.124

AC:

18886

AN:

152108

Hom.:

1534

Cov.:

AF XY:

0.122

AC XY:

9049

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.232

AC:

9604

AN:

41456

American (AMR)

AF:

0.0903

AC:

1381

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3472

East Asian (EAS)

AF:

0.0235

AC:

121

AN:

5156

South Asian (SAS)

AF:

0.117

AC:

565

AN:

4812

European-Finnish (FIN)

AF:

0.0379

AC:

402

AN:

10610

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0869

AC:

5912

AN:

68008

Other (OTH)

AF:

0.135

AC:

284

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

807

1613

2420

3226

4033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.114

Hom.:

753

Bravo

AF:

0.131

Asia WGS

AF:

0.0750

AC:

263

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Drash syndrome (2)

not provided (2)

Wilms tumor 1 (2)

Frasier syndrome (1)

Meacham syndrome (1)

Nephrotic syndrome, type 4 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.2

(source)

DANN

Benign

0.72

PhyloP100

0.27

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

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