chr11-32417492-T-C

Variant names:

• chr11-32417492-T-C
• rs2295081
• ENST00000379077.9:n.*81A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000379077.9(WT1):​n.*81A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,265,104 control chromosomes in the GnomAD database, including 62,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10598 hom., cov: 32)
  • Exomes 𝑓: 0.28 (51410 hom.)
• Consequence: WT1 ENST00000379077.9 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.70
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-32417492-T-C is Benign according to our data. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-32417492-T-C is described in CliVar as Benign. Clinvar id is 1226513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.965+85A>G		intron_variant	Intron 4 of 9	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10	c.965+85A>G		intron_variant	Intron 4 of 9	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52446 AN: 151934 Hom.: 10564 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.279 AC: 310620 AN: 1113052 Hom.: 51410 Cov.: 15 AF XY: 0.285 AC XY: 161927 AN XY: 568508

African (AFR) AF: 0.489 AC: 12652 AN: 25896

American (AMR) AF: 0.426 AC: 17833 AN: 41860

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8128 AN: 23806

East Asian (EAS) AF: 0.685 AC: 25511 AN: 37242

South Asian (SAS) AF: 0.484 AC: 37050 AN: 76522

European-Finnish (FIN) AF: 0.216 AC: 11202 AN: 51958

Middle Eastern (MID) AF: 0.352 AC: 1791 AN: 5094

European-Non Finnish (NFE) AF: 0.226 AC: 181236 AN: 801972

Other (OTH) AF: 0.312 AC: 15217 AN: 48702

GnomAD4 genome AF: 0.345 AC: 52523 AN: 152052 Hom.: 10598 Cov.: 32 AF XY: 0.353 AC XY: 26215 AN XY: 74336

African (AFR) AF: 0.485 AC: 20107 AN: 41436

American (AMR) AF: 0.396 AC: 6053 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3472

East Asian (EAS) AF: 0.724 AC: 3749 AN: 5176

South Asian (SAS) AF: 0.512 AC: 2462 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2326 AN: 10592

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15600 AN: 67964

Other (OTH) AF: 0.363 AC: 768 AN: 2114

Alfa AF: 0.290 Hom.: 984

Bravo AF: 0.364

Asia WGS AF: 0.635 AC: 2206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 57% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 53. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.35
PhyloP100		-1.7
PromoterAI		0.0024	Neutral
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: rs2295081; hg19: chr11-32439038; COSMIC: COSV60068824;