rs5030168

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024426.6(WT1):c.785-20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,582,834 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 21 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.904

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=-0.79).

BP6

Variant 11-32428078-C-A is Benign according to our data. Variant chr11-32428078-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 261715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32428078-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0061 (930/152346) while in subpopulation AFR AF= 0.0212 (883/41580). AF 95% confidence interval is 0.0201. There are 9 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 930 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1	NM_024426.6 linkuse as main transcript	c.785-20G>T		intron_variant		ENST00000452863.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1	ENST00000452863.10 linkuse as main transcript	c.785-20G>T		intron_variant		1	NM_024426.6		P19544-7

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

931

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00166

AC:

362

AN:

218550

Hom.:

AF XY:

0.00125

AC XY:

149

AN XY:

118920

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.000705

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000739

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000624

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000678

AC:

970

AN:

1430488

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

409

AN XY:

706706

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.000859

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000361

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000265

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00610

AC:

930

AN:

152346

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0212

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00538

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2017	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. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 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

- -

Wilms tumor 1

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

-0.79

CADD

Benign

2.4

DANN

Benign

0.56

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