11-32388003-AACACACACACACACACACAC-AACACACACACACACACAC

Variant names:

• chr11-32388003-AAC-A
• rs58549495
• NM_024426.6:c.*1053_*1054delGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_024426.6(WT1):​c.*1053_*1054delGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 221,548 control chromosomes in the GnomAD database, including 195 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.036 (195 hom., cov: 0)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: WT1 NM_024426.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.*1053_*1054delGT		3_prime_UTR_variant	Exon 10 of 10	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863	c.*1053_*1054delGT		3_prime_UTR_variant	Exon 10 of 10	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5274 AN: 145978 Hom.: 195 Cov.: 0

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0319

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00994

Gnomad MID AF: 0.0581

Gnomad NFE AF: 0.00885

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.134 AC: 10117 AN: 75460 Hom.: 0 AF XY: 0.137 AC XY: 4747 AN XY: 34754

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.0971

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.0773

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.0362 AC: 5288 AN: 146088 Hom.: 195 Cov.: 0 AF XY: 0.0354 AC XY: 2513 AN XY: 71018

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.0319

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0171

Gnomad4 FIN AF: 0.00994

Gnomad4 NFE AF: 0.00888

Gnomad4 OTH AF: 0.0330

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: rs58549495; hg19: chr11-32409549;