Variant rs5030171 details in Genebe, Genetics Data Aggregator

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+85G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,360,870 control chromosomes in the GnomAD database, including 33,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4467 hom., cov: 33)

Exomes 𝑓: 0.18 ( 28651 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.571

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=-0.8).

BP6

Variant 11-32427871-C-G is Benign according to our data. Variant chr11-32427871-C-G is described in ClinVar as [Benign]. Clinvar id is 1242813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32427871-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1	NM_024426.6 linkuse as main transcript	c.887+85G>C		intron_variant		ENST00000452863.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1	ENST00000452863.10 linkuse as main transcript	c.887+85G>C		intron_variant		1	NM_024426.6		P19544-7

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32138

AN:

151854

Hom.:

4437

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.183

AC:

221538

AN:

1208900

Hom.:

28651

AF XY:

0.188

AC XY:

111770

AN XY:

594092

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.374

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.691

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.212

AC:

32208

AN:

151970

Hom.:

4467

Cov.:

AF XY:

0.222

AC XY:

16512

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.716

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.172

Hom.:

301

Bravo

AF:

0.222

Asia WGS

AF:

0.581

AC:

2017

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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 25% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.5

DANN

Benign

0.51

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