chr11-32388003-AAC-A

Variant names:

• chr11-32388003-AAC-A
• rs58549495
• ENST00000379077.9:n.*1806_*1807delGT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

WT1 Gene-Disease associations (from GenCC):

• Denys-Drash syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P
• Wilms tumor 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Frasier syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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	ENST00000452863.10	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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.130 AC: 494 AN: 3794

American (AMR) AF: 0.0971 AC: 231 AN: 2378

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 714 AN: 4690

East Asian (EAS) AF: 0.0434 AC: 488 AN: 11238

South Asian (SAS) AF: 0.0773 AC: 51 AN: 660

European-Finnish (FIN) AF: 0.133 AC: 95 AN: 716

Middle Eastern (MID) AF: 0.146 AC: 65 AN: 444

European-Non Finnish (NFE) AF: 0.156 AC: 7067 AN: 45332

Other (OTH) AF: 0.147 AC: 912 AN: 6208

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0997 AC: 4006 AN: 40180

American (AMR) AF: 0.0179 AC: 263 AN: 14684

Ashkenazi Jewish (ASJ) AF: 0.0319 AC: 108 AN: 3384

East Asian (EAS) AF: 0.0147 AC: 73 AN: 4968

South Asian (SAS) AF: 0.0171 AC: 78 AN: 4558

European-Finnish (FIN) AF: 0.00994 AC: 93 AN: 9356

Middle Eastern (MID) AF: 0.0559 AC: 16 AN: 286

European-Non Finnish (NFE) AF: 0.00888 AC: 584 AN: 65758

Other (OTH) AF: 0.0330 AC: 67 AN: 2030

Alfa AF: 0.00311 Hom.: 53

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs58549495; hg19: chr11-32409549;