chr11-32427874-C-A

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+82G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,383,662 control chromosomes in the GnomAD database, including 33,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4470 hom., cov: 33)

Exomes 𝑓: 0.18 ( 29021 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0860

Publications

5 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=-0.8).

BP6

Variant 11-32427874-C-A is Benign according to our data. Variant chr11-32427874-C-A is described in ClinVar as Benign. ClinVar VariationId is 1292784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6 link	c.887+82G>T		intron_variant	Intron 3 of 9	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10 link	c.887+82G>T		intron_variant	Intron 3 of 9	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32144

AN:

151888

Hom.:

4440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.183

AC:

225260

AN:

1231656

Hom.:

29021

AF XY:

0.188

AC XY:

113628

AN XY:

605058

show subpopulations

African (AFR)

AF:

0.206

AC:

5882

AN:

28594

American (AMR)

AF:

0.374

AC:

11337

AN:

30318

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

3701

AN:

20908

East Asian (EAS)

AF:

0.691

AC:

24482

AN:

35434

South Asian (SAS)

AF:

0.387

AC:

26719

AN:

68994

European-Finnish (FIN)

AF:

0.179

AC:

8139

AN:

45396

Middle Eastern (MID)

AF:

0.210

AC:

762

AN:

3624

European-Non Finnish (NFE)

AF:

0.141

AC:

133260

AN:

946684

Other (OTH)

AF:

0.212

AC:

10978

AN:

51704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7927

15853

23780

31706

39633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5160

10320

15480

20640

25800

<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:

0.212

AC:

32214

AN:

152006

Hom.:

4470

Cov.:

AF XY:

0.222

AC XY:

16511

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.201

AC:

8350

AN:

41478

American (AMR)

AF:

0.317

AC:

4839

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

588

AN:

3466

East Asian (EAS)

AF:

0.716

AC:

3652

AN:

5104

South Asian (SAS)

AF:

0.425

AC:

2040

AN:

4798

European-Finnish (FIN)

AF:

0.187

AC:

1975

AN:

10586

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10028

AN:

67986

Other (OTH)

AF:

0.229

AC:

483

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1243

2485

3728

4970

6213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.0858

Hom.:

114

Bravo

AF:

0.222

Asia WGS

AF:

0.581

AC:

2017

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 29. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.6

(source)

DANN

Benign

0.64

PhyloP100

0.086

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

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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