11-32402843-C-G

Variant names:

• chr11-32402843-C-G
• rs5030240
• NM_024426.6:c.1017-2799G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024426.6(WT1):​c.1017-2799G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,158 control chromosomes in the GnomAD database, including 6,497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6497 hom., cov: 33)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.1017-2799G>C		intron_variant	Intron 5 of 9	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10	c.1017-2799G>C		intron_variant	Intron 5 of 9	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41821 AN: 152040 Hom.: 6481 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41867 AN: 152158 Hom.: 6497 Cov.: 33 AF XY: 0.284 AC XY: 21107 AN XY: 74394

African (AFR) AF: 0.305 AC: 12643 AN: 41506

American (AMR) AF: 0.355 AC: 5423 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3505 AN: 5174

South Asian (SAS) AF: 0.418 AC: 2020 AN: 4828

European-Finnish (FIN) AF: 0.216 AC: 2283 AN: 10592

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14141 AN: 67988

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.0327 Hom.: 86

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.21
PhyloP100		-1.7
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: rs5030240; hg19: chr11-32424389;