rs760304811

Positions:

• chr11-32434938-AGGC-A
• chr11-32434938-AGGC-AGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP3 BS2_Supporting

The NM_024426.6(WT1):​c.420_422del​(p.Pro141del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,436,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WT1 NM_024426.6 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.05

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 Likely_benign. Variant got -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_024426.6
• BS2: High AC in GnomAdExome4 at 28 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WT1	NM_024426.6	c.420_422del	p.Pro141del	inframe_deletion	1/10	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10	c.420_422del	p.Pro141del	inframe_deletion	1/10	1	NM_024426.6	ENSP00000415516

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000195 AC: 28 AN: 1436548 Hom.: 0 AF XY: 0.0000280 AC XY: 20 AN XY: 713326

Gnomad4 AFR exome AF: 0.000182

Gnomad4 AMR exome AF: 0.0000241

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.0000772

Gnomad4 SAS exome AF: 0.0000238

Gnomad4 FIN exome AF: 0.0000846

Gnomad4 NFE exome AF: 0.00000907

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74154

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00106 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs760304811; hg19: chr11-32456484;