chr11-32427940-C-T

Variant names:

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.887+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,601,882 control chromosomes in the GnomAD database, including 29,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 8294 hom., cov: 33)

Exomes 𝑓: 0.15 ( 21634 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.132

Publications

8 publications found

Variant links:

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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
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=-0.76).

BP6

Variant 11-32427940-C-T is Benign according to our data. Variant chr11-32427940-C-T is described in ClinVar as Benign. ClinVar VariationId is 261716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 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
WT1	NM_024426.6	MANE Select	c.887+16G>A	intron	N/A	NP_077744.4
WT1	NM_024424.5		c.887+16G>A	intron	N/A	NP_077742.3
WT1	NM_001407044.1		c.887+16G>A	intron	N/A	NP_001393973.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WT1	ENST00000452863.10	TSL:1 MANE Select	c.887+16G>A	intron	N/A	ENSP00000415516.5
WT1	ENST00000639563.4	TSL:1	c.887+16G>A	intron	N/A	ENSP00000492269.3
WT1	ENST00000332351.9	TSL:1	c.887+16G>A	intron	N/A	ENSP00000331327.5

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39274

AN:

152050

Hom.:

8276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.0670

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.0335

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.163

AC:

37700

AN:

231494

AF XY:

0.161

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.0919

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.0815

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.153

AC:

221854

AN:

1449714

Hom.:

21634

Cov.:

AF XY:

0.155

AC XY:

111354

AN XY:

719888

show subpopulations

African (AFR)

AF:

0.599

AC:

19942

AN:

33286

American (AMR)

AF:

0.101

AC:

4379

AN:

43472

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5446

AN:

25780

East Asian (EAS)

AF:

0.0468

AC:

1843

AN:

39400

South Asian (SAS)

AF:

0.223

AC:

18826

AN:

84588

European-Finnish (FIN)

AF:

0.0809

AC:

4224

AN:

52244

Middle Eastern (MID)

AF:

0.261

AC:

1158

AN:

4438

European-Non Finnish (NFE)

AF:

0.141

AC:

155752

AN:

1106760

Other (OTH)

AF:

0.172

AC:

10284

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

9378

18756

28135

37513

46891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5816

11632

17448

23264

29080

<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:

0.258

AC:

39331

AN:

152168

Hom.:

8294

Cov.:

AF XY:

0.253

AC XY:

18807

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.584

AC:

24214

AN:

41496

American (AMR)

AF:

0.156

AC:

2382

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

667

AN:

3472

East Asian (EAS)

AF:

0.0335

AC:

173

AN:

5158

South Asian (SAS)

AF:

0.205

AC:

988

AN:

4810

European-Finnish (FIN)

AF:

0.0774

AC:

821

AN:

10602

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9399

AN:

68014

Other (OTH)

AF:

0.253

AC:

535

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1140

2281

3421

4562

5702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.176

Hom.:

1323

Bravo

AF:

0.275

Asia WGS

AF:

0.127

AC:

443

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Wilms tumor 1 (2)

11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 (1)

Drash syndrome (1)

Frasier syndrome (1)

Meacham syndrome (1)

Nephrotic syndrome, type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.8

(source)

DANN

Benign

0.88

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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