rs5030170

Variant names:

• chr11-32427874-C-A
• rs5030170
• NM_024426.6:c.887+82G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-32427874-C-A
• chr11-32427874-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024426.6(WT1):​c.887+82G>T 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 1,383,662 control chromosomes in the GnomAD database, including 33,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4470 hom., cov: 33)
  • Exomes 𝑓: 0.18 (29021 hom.)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0860
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Denys-Drash syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
• Wilms tumor 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Frasier syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-32427874-C-A is Benign according to our data. Variant chr11-32427874-C-A is described in ClinVar as Benign. ClinVar VariationId is 1292784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.887+82G>T		intron_variant	Intron 3 of 9	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10	c.887+82G>T		intron_variant	Intron 3 of 9	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32144 AN: 151888 Hom.: 4440 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.210

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: 0.148

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.183 AC: 225260 AN: 1231656 Hom.: 29021 AF XY: 0.188 AC XY: 113628 AN XY: 605058

African (AFR) AF: 0.206 AC: 5882 AN: 28594

American (AMR) AF: 0.374 AC: 11337 AN: 30318

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 3701 AN: 20908

East Asian (EAS) AF: 0.691 AC: 24482 AN: 35434

South Asian (SAS) AF: 0.387 AC: 26719 AN: 68994

European-Finnish (FIN) AF: 0.179 AC: 8139 AN: 45396

Middle Eastern (MID) AF: 0.210 AC: 762 AN: 3624

European-Non Finnish (NFE) AF: 0.141 AC: 133260 AN: 946684

Other (OTH) AF: 0.212 AC: 10978 AN: 51704

GnomAD4 genome AF: 0.212 AC: 32214 AN: 152006 Hom.: 4470 Cov.: 33 AF XY: 0.222 AC XY: 16511 AN XY: 74292

African (AFR) AF: 0.201 AC: 8350 AN: 41478

American (AMR) AF: 0.317 AC: 4839 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3466

East Asian (EAS) AF: 0.716 AC: 3652 AN: 5104

South Asian (SAS) AF: 0.425 AC: 2040 AN: 4798

European-Finnish (FIN) AF: 0.187 AC: 1975 AN: 10586

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10028 AN: 67986

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.0858 Hom.: 114

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 31% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 29. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030170; hg19: chr11-32449420; COSMIC: COSV60078237;