dbSNP rs2234585: WT1:c.785-57C>T (chr11-32428115-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024426.6(WT1):c.785-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,478,162 control chromosomes in the GnomAD database, including 35,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4535 hom., cov: 33)

Exomes 𝑓: 0.18 ( 31199 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.500

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-32428115-G-A is Benign according to our data. Variant chr11-32428115-G-A is described in ClinVar as [Benign]. Clinvar id is 1292785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32428115-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6 link	c.785-57C>T		intron_variant	Intron 2 of 9	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.785-57C>T		intron_variant	Intron 2 of 9	1	NM_024426.6	ENSP00000415516.5		P19544-7A0A0A0MT54

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32269

AN:

152062

Hom.:

4505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.718

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.184

AC:

244490

AN:

1325982

Hom.:

31199

AF XY:

0.189

AC XY:

122837

AN XY:

650402

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.693

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.143

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.213

AC:

32340

AN:

152180

Hom.:

4535

Cov.:

AF XY:

0.223

AC XY:

16576

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.718

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.172

Hom.:

302

Bravo

AF:

0.222

Asia WGS

AF:

0.581

AC:

2020

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

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

DANN

Benign

0.78

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