11-32388003-AACACACACACACACACACAC-AACACACACACAC

Variant names:

• chr11-32388003-AACACACAC-A
• rs58549495
• NM_024426.6:c.*1047_*1054delGTGTGTGT

Variant summary

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

The NM_024426.6(WT1):​c.*1047_*1054delGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 225,564 control chromosomes in the GnomAD database, including 78 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (76 hom., cov: 0)
  • Exomes 𝑓: 0.055 (2 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.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.*1047_*1054delGTGTGTGT		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.*1047_*1054delGTGTGTGT		3_prime_UTR_variant	Exon 10 of 10	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4327 AN: 146388 Hom.: 76 Cov.: 0

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0305

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.00744

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0438

GnomAD4 exome AF: 0.0555 AC: 4385 AN: 79064 Hom.: 2 AF XY: 0.0535 AC XY: 1960 AN XY: 36652

Gnomad4 AFR exome AF: 0.0431

Gnomad4 AMR exome AF: 0.0723

Gnomad4 ASJ exome AF: 0.0636

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.0271

Gnomad4 FIN exome AF: 0.0420

Gnomad4 NFE exome AF: 0.0426

Gnomad4 OTH exome AF: 0.0503

GnomAD4 genome AF: 0.0296 AC: 4331 AN: 146500 Hom.: 76 Cov.: 0 AF XY: 0.0287 AC XY: 2044 AN XY: 71242

Gnomad4 AFR AF: 0.0205

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.00723

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0434

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;