11-32388003-AACACACACACACACACACAC-AACACACACAC

Variant names:

• chr11-32388003-AACACACACAC-A
• rs58549495
• NM_024426.6:c.*1045_*1054delGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024426.6(WT1):​c.*1045_*1054delGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 229,128 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: WT1 NM_024426.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00373 (547/146582) while in subpopulation AFR AF= 0.0113 (454/40230). AF 95% confidence interval is 0.0104. There are 4 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.*1045_*1054delGTGTGTGTGT		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.*1045_*1054delGTGTGTGTGT		3_prime_UTR_variant	Exon 10 of 10	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 540 AN: 146466 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00293

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00161

Gnomad SAS AF: 0.000438

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000455

Gnomad OTH AF: 0.00249

GnomAD4 exome AF: 0.00131 AC: 108 AN: 82546 Hom.: 0 AF XY: 0.00126 AC XY: 48 AN XY: 38124

Gnomad4 AFR exome AF: 0.00926

Gnomad4 AMR exome AF: 0.00359

Gnomad4 ASJ exome AF: 0.00137

Gnomad4 EAS exome AF: 0.000435

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00133

Gnomad4 NFE exome AF: 0.000748

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00373 AC: 547 AN: 146582 Hom.: 4 Cov.: 0 AF XY: 0.00351 AC XY: 250 AN XY: 71292

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.00292

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.00161

Gnomad4 SAS AF: 0.000438

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000455

Gnomad4 OTH AF: 0.00246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;