11-32427940-C-T

Position:

chr11-32427940-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

WT1 (HGNC:):

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=-0.76).

BP6

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 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.887+16G>A		intron_variant		ENST00000452863.10	NP_077744.4	P19544-7Q6PI38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10 linkuse as main transcript	c.887+16G>A		intron_variant		1	NM_024426.6	ENSP00000415516.5		P19544-7A0A0A0MT54

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

GnomAD3 exomes

AF:

0.163

AC:

37700

AN:

231494

Hom.:

4880

AF XY:

0.161

AC XY:

20303

AN XY:

125934

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 SAS exome

AF:

0.219

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

Gnomad4 AFR exome

AF:

0.599

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.0468

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.0809

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.258

AC:

39331

AN:

152168

Hom.:

8294

Cov.:

AF XY:

0.253

AC XY:

18807

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.584

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.0335

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.253

Alfa

AF:

0.175

Hom.:

1204

Bravo

AF:

0.275

Asia WGS

AF:

0.127

AC:

443

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

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	GeneDx	Apr 05, 2016	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 26, 2016	Variant summary: The WT1 c.872+16G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 18201/82628 control chromosomes (2511 homozygotes), predominantly observed in the South Asian subpopulation at a frequency of 0.6155869 (5150/8366). This frequency is about 65662 times the estimated maximal expected allele frequency of a pathogenic WT1 variant (0.0000094), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. Taken together, this variant is classified as benign. -
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	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

-0.76

CADD

Benign

5.8

DANN

Benign

0.88

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

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