NM_024426.6:c.1016+337A>G

Variant names:

• chr11-32416153-T-C
• rs3858444
• NM_024426.6:c.1016+337A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024426.6(WT1):​c.1016+337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,204 control chromosomes in the GnomAD database, including 53,336 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (53336 hom., cov: 33)
• Consequence: WT1 NM_024426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WT1	NM_024426.6	c.1016+337A>G		intron_variant	Intron 5 of 9	ENST00000452863.10	NP_077744.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WT1	ENST00000452863.10	c.1016+337A>G		intron_variant	Intron 5 of 9	1	NM_024426.6	ENSP00000415516.5

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126281 AN: 152086 Hom.: 53272 Cov.: 33

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.832

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.830 AC: 126404 AN: 152204 Hom.: 53336 Cov.: 33 AF XY: 0.830 AC XY: 61749 AN XY: 74406

African (AFR) AF: 0.960 AC: 39876 AN: 41548

American (AMR) AF: 0.860 AC: 13151 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5174

South Asian (SAS) AF: 0.926 AC: 4474 AN: 4830

European-Finnish (FIN) AF: 0.676 AC: 7151 AN: 10580

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51150 AN: 67996

Other (OTH) AF: 0.834 AC: 1762 AN: 2112

Alfa AF: 0.773 Hom.: 36971

Bravo AF: 0.848

Asia WGS AF: 0.967 AC: 3361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		0.094
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: rs3858444; hg19: chr11-32437699;