chr11-32427871-C-G

Variant names:

• chr11-32427871-C-G
• rs5030171
• NM_024426.6:c.887+85G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.571
• Publications: 6 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=-0.8).
• BP6: Variant 11-32427871-C-G is Benign according to our data. Variant chr11-32427871-C-G is described in ClinVar as Benign. ClinVar VariationId is 1242813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024426.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WT1	NM_024426.6	MANE Select	c.887+85G>C		intron	N/A	NP_077744.4
	WT1	NM_024424.5		c.887+85G>C		intron	N/A	NP_077742.3
	WT1	NM_001407044.1		c.887+85G>C		intron	N/A	NP_001393973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WT1	ENST00000452863.10	TSL:1 MANE Select	c.887+85G>C		intron	N/A	ENSP00000415516.5
	WT1	ENST00000639563.4	TSL:1	c.887+85G>C		intron	N/A	ENSP00000492269.3
	WT1	ENST00000332351.9	TSL:1	c.887+85G>C		intron	N/A	ENSP00000331327.5

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

African (AFR) AF: 0.206 AC: 5765 AN: 28048

American (AMR) AF: 0.374 AC: 11181 AN: 29878

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 3638 AN: 20562

East Asian (EAS) AF: 0.691 AC: 24310 AN: 35186

South Asian (SAS) AF: 0.388 AC: 26357 AN: 67968

European-Finnish (FIN) AF: 0.180 AC: 8073 AN: 44938

Middle Eastern (MID) AF: 0.211 AC: 752 AN: 3558

European-Non Finnish (NFE) AF: 0.141 AC: 130657 AN: 927874

Other (OTH) AF: 0.212 AC: 10805 AN: 50888

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

African (AFR) AF: 0.201 AC: 8350 AN: 41444

American (AMR) AF: 0.317 AC: 4840 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3468

East Asian (EAS) AF: 0.716 AC: 3649 AN: 5098

South Asian (SAS) AF: 0.425 AC: 2040 AN: 4800

European-Finnish (FIN) AF: 0.187 AC: 1974 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10027 AN: 67996

Other (OTH) AF: 0.228 AC: 482 AN: 2110

Alfa AF: 0.172 Hom.: 301

Bravo AF: 0.222

Asia WGS AF: 0.581 AC: 2017 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.5
DANN	Benign	0.51
PhyloP100		0.57
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: rs5030171; hg19: chr11-32449417; COSMIC: COSV60078230;