rs5030171

chr11-32427871-C-Gchr11-32427871-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024426.6(WT1):c.887+85G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,360,870 control chromosomes in the GnomAD database, including 33,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4467 hom., cov: 33)
  • Exomes 𝑓: 0.18 (28651 hom.)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.571

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-32427871-C-G is Benign according to our data. Variant chr11-32427871-C-G is described in ClinVar as [Benign]. Clinvar id is 1242813.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-32427871-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WT1	NM_024426.6	c.887+85G>C		intron_variant		ENST00000452863.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WT1	ENST00000452863.10	c.887+85G>C		intron_variant		1	NM_024426.6

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32138 AN: 151854 Hom.: 4437 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.183 AC: 221538 AN: 1208900 Hom.: 28651 AF XY: 0.188 AC XY: 111770 AN XY: 594092

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.691

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.212 AC: 32208 AN: 151970 Hom.: 4467 Cov.: 33 AF XY: 0.222 AC XY: 16512 AN XY: 74274

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.228

Alfa AF: 0.172 Hom.: 301

Bravo AF: 0.222

Asia WGS AF: 0.581 AC: 2017 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.5
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs5030171; hg19: chr11-32449417; COSMIC: COSV60078230;