11-32388003-AACAC-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_024426.6(WT1):c.*1051_*1054delGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 228,700 control chromosomes in the GnomAD database, including 2,641 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.16 ( 2633 hom., cov: 0)

Exomes 𝑓: 0.10 ( 8 hom. )

Consequence

WT1
NM_024426.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:8

Conservation

PhyloP100: 1.60

Publications

2 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6 link	c.1051_1054delGTGT		3_prime_UTR_variant	Exon 10 of 10	ENST00000452863.10	NP_077744.4	P19544-7Q6PI38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10 link	c.1051_1054delGTGT		3_prime_UTR_variant	Exon 10 of 10	1	NM_024426.6	ENSP00000415516.5		P19544-7A0A0A0MT54

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

23793

AN:

146316

Hom.:

2627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.0279

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0736

Gnomad MID

AF:

0.181

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.102

AC:

8400

AN:

82268

Hom.:

AF XY:

0.100

AC XY:

3817

AN XY:

37998

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.261

AC:

1006

AN:

3852

American (AMR)

AF:

0.0866

AC:

217

AN:

2506

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

622

AN:

5110

East Asian (EAS)

AF:

0.0159

AC:

182

AN:

11482

South Asian (SAS)

AF:

0.123

AC:

AN:

690

European-Finnish (FIN)

AF:

0.0745

AC:

AN:

752

Middle Eastern (MID)

AF:

0.142

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.106

AC:

5378

AN:

50608

Other (OTH)

AF:

0.116

AC:

784

AN:

6776

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

472

944

1415

1887

2359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.163

AC:

23823

AN:

146432

Hom.:

2633

Cov.:

AF XY:

0.161

AC XY:

11453

AN XY:

71216

show subpopulations

African (AFR)

AF:

0.319

AC:

12822

AN:

40180

American (AMR)

AF:

0.107

AC:

1567

AN:

14702

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

424

AN:

3386

East Asian (EAS)

AF:

0.0282

AC:

140

AN:

4970

South Asian (SAS)

AF:

0.131

AC:

596

AN:

4550

European-Finnish (FIN)

AF:

0.0736

AC:

705

AN:

9574

Middle Eastern (MID)

AF:

0.164

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.108

AC:

7120

AN:

65872

Other (OTH)

AF:

0.151

AC:

306

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

870

1739

2609

3478

4348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0500

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:8

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephroblastoma

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

11p partial monosomy syndrome

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Meacham syndrome

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephrotic syndrome, type 4

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

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.

11-32388003-AACAC-A

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