rs1799937

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.1448-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,612,978 control chromosomes in the GnomAD database, including 75,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11403 hom., cov: 32)

Exomes 𝑓: 0.27 ( 64340 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.842

Publications

21 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=-0.84).

BP6

Variant 11-32389228-A-G is Benign according to our data. Variant chr11-32389228-A-G is described in ClinVar as Benign. ClinVar VariationId is 261709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 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.1448-49T>C	intron	N/A	NP_077744.4
WT1	NM_024424.5		c.1439-49T>C	intron	N/A	NP_077742.3
WT1	NM_001407044.1		c.1433-49T>C	intron	N/A	NP_001393973.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WT1	ENST00000452863.10	TSL:1 MANE Select	c.1448-49T>C	intron	N/A	ENSP00000415516.5
WT1	ENST00000639563.4	TSL:1	c.1397-49T>C	intron	N/A	ENSP00000492269.3
WT1	ENST00000332351.9	TSL:1	c.1388-49T>C	intron	N/A	ENSP00000331327.5

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53974

AN:

151906

Hom.:

11372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.726

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.359

GnomAD2 exomes

AF:

0.349

AC:

87480

AN:

250408

AF XY:

0.346

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.722

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.275

AC:

401202

AN:

1460954

Hom.:

64340

Cov.:

AF XY:

0.279

AC XY:

202853

AN XY:

726788

show subpopulations

African (AFR)

AF:

0.533

AC:

17845

AN:

33460

American (AMR)

AF:

0.427

AC:

19063

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8729

AN:

26126

East Asian (EAS)

AF:

0.686

AC:

27208

AN:

39686

South Asian (SAS)

AF:

0.479

AC:

41261

AN:

86214

European-Finnish (FIN)

AF:

0.217

AC:

11533

AN:

53212

Middle Eastern (MID)

AF:

0.349

AC:

2007

AN:

5758

European-Non Finnish (NFE)

AF:

0.229

AC:

254620

AN:

1111472

Other (OTH)

AF:

0.314

AC:

18936

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

14959

29918

44877

59836

74795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9332

18664

27996

37328

46660

<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:

0.355

AC:

54044

AN:

152024

Hom.:

11403

Cov.:

AF XY:

0.363

AC XY:

26948

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.523

AC:

21660

AN:

41422

American (AMR)

AF:

0.395

AC:

6042

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1129

AN:

3470

East Asian (EAS)

AF:

0.725

AC:

3748

AN:

5168

South Asian (SAS)

AF:

0.506

AC:

2430

AN:

4802

European-Finnish (FIN)

AF:

0.222

AC:

2355

AN:

10600

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15590

AN:

67962

Other (OTH)

AF:

0.368

AC:

776

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1618

3237

4855

6474

8092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.323

Hom.:

2543

Bravo

AF:

0.376

Asia WGS

AF:

0.632

AC:

2198

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)

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

-0.84

CADD

Benign

0.0050

(source)

DANN

Benign

0.44

PhyloP100

-0.84

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over