rs1799937

Positions:

chr11-32389228-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 261709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32389228-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WT1	NM_024426.6 linkuse as main transcript	c.1448-49T>C		intron_variant		ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10 linkuse as main transcript	c.1448-49T>C		intron_variant		1	NM_024426.6	ENSP00000415516		P19544-7

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

GnomAD3 exomes

AF:

0.349

AC:

87480

AN:

250408

Hom.:

18430

AF XY:

0.346

AC XY:

46902

AN XY:

135376

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 SAS exome

AF:

0.485

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

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.686

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.355

AC:

54044

AN:

152024

Hom.:

11403

Cov.:

AF XY:

0.363

AC XY:

26948

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.319

Hom.:

2438

Bravo

AF:

0.376

Asia WGS

AF:

0.632

AC:

2198

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 54. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Wilms tumor 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

Frasier syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Meacham syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Nephrotic syndrome, type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Drash syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0050

DANN

Benign

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over