rs5030240

Positions:

• chr11-32402843-C-A
• chr11-32402843-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024426.6(WT1):​c.1017-2799G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,158 control chromosomes in the GnomAD database, including 2,949 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 0.16 (2949 hom., cov: 33)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1	NM_024426.6	c.1017-2799G>T		intron_variant		ENST00000452863.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1	ENST00000452863.10	c.1017-2799G>T		intron_variant		1	NM_024426.6

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24076 AN: 152040 Hom.: 2940 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0608

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.159 AC: 24118 AN: 152158 Hom.: 2949 Cov.: 33 AF XY: 0.153 AC XY: 11347 AN XY: 74390

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.0841

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.0462

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.0608

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0749 Hom.: 86

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs5030240; hg19: chr11-32424389;