11-32388079-A-AT

Variant names:

• chr11-32388079-A-AT
• rs5030326
• ENST00000379077.9:n.*1731dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024426.6(WT1):​c.*978dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 236,018 control chromosomes in the GnomAD database, including 5,177 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2695 hom., cov: 30)
  • Exomes 𝑓: 0.19 (2482 hom.)
• Consequence: WT1 NM_024426.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.165
• Publications: 3 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 -10 ACMG points.

• BP6: Variant 11-32388079-A-AT is Benign according to our data. Variant chr11-32388079-A-AT is described in ClinVar as [Benign]. Clinvar id is 304383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.*978dupA		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.*978dupA		3_prime_UTR_variant	Exon 10 of 10	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22387 AN: 151496 Hom.: 2681 Cov.: 30

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.187 AC: 15817 AN: 84404 Hom.: 2482 Cov.: 0 AF XY: 0.182 AC XY: 7121 AN XY: 39076

African (AFR) AF: 0.0602 AC: 237 AN: 3940

American (AMR) AF: 0.306 AC: 777 AN: 2542

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 697 AN: 5174

East Asian (EAS) AF: 0.556 AC: 6484 AN: 11664

South Asian (SAS) AF: 0.302 AC: 215 AN: 712

European-Finnish (FIN) AF: 0.117 AC: 107 AN: 916

Middle Eastern (MID) AF: 0.127 AC: 64 AN: 502

European-Non Finnish (NFE) AF: 0.119 AC: 6192 AN: 52028

Other (OTH) AF: 0.151 AC: 1044 AN: 6926

GnomAD4 genome AF: 0.148 AC: 22409 AN: 151614 Hom.: 2695 Cov.: 30 AF XY: 0.159 AC XY: 11805 AN XY: 74088

African (AFR) AF: 0.0618 AC: 2558 AN: 41376

American (AMR) AF: 0.263 AC: 3997 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3458

East Asian (EAS) AF: 0.657 AC: 3372 AN: 5136

South Asian (SAS) AF: 0.302 AC: 1443 AN: 4780

European-Finnish (FIN) AF: 0.177 AC: 1854 AN: 10460

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8241 AN: 67876

Other (OTH) AF: 0.158 AC: 332 AN: 2106

Alfa AF: 0.0640 Hom.: 63

Asia WGS AF: 0.436 AC: 1514 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Nephroblastoma Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meacham syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nephrotic syndrome, type 4 Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
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: rs5030326; hg19: chr11-32409625; COSMIC: COSV60072466; COSMIC: COSV60072466;