rs2234591

Positions:

• chr11-32399873-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024426.6(WT1):​c.1113+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,508,790 control chromosomes in the GnomAD database, including 3 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 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (3 hom.)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAd4 at 203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1	NM_024426.6	c.1113+75A>G		intron_variant		ENST00000452863.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1	ENST00000452863.10	c.1113+75A>G		intron_variant		1	NM_024426.6

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 203 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00181 AC: 2453 AN: 1356560 Hom.: 3 AF XY: 0.00175 AC XY: 1186 AN XY: 677420

Gnomad4 AFR exome AF: 0.000321

Gnomad4 AMR exome AF: 0.000830

Gnomad4 ASJ exome AF: 0.00313

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000561

Gnomad4 NFE exome AF: 0.00215

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.00133 AC: 203 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00128 AC XY: 95 AN XY: 74422

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.38

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: rs2234591; hg19: chr11-32421419;