rs2295081

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024426.6(WT1):c.965+85A>G variant causes a intron 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
NM_024426.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.70

Publications

9 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), ClinGen, G2P
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Frasier syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 ClinVar as Benign. ClinVar VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WT1	NM_024426.6	MANE Select	c.965+85A>G	intron	N/A	NP_077744.4
WT1	NM_024424.5		c.965+85A>G	intron	N/A	NP_077742.3	H0Y7K5
WT1	NM_001407044.1		c.965+85A>G	intron	N/A	NP_001393973.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WT1	ENST00000452863.10	TSL:1 MANE Select	c.965+85A>G	intron	N/A	ENSP00000415516.5	P19544-7
WT1	ENST00000639563.4	TSL:1	c.965+85A>G	intron	N/A	ENSP00000492269.3	P19544-8
WT1	ENST00000332351.9	TSL:1	c.965+85A>G	intron	N/A	ENSP00000331327.5	J3KNN9

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52446

AN:

151934

Hom.:

10564

Cov.:

show subpopulations

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.:

AF XY:

0.285

AC XY:

161927

AN XY:

568508

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

10518

21035

31553

42070

52588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5800

11600

17400

23200

29000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.345

AC:

52523

AN:

152052

Hom.:

10598

Cov.:

AF XY:

0.353

AC XY:

26215

AN XY:

74336

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1643

3285

4928

6570

8213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.290

Hom.:

984

Bravo

AF:

0.364

Asia WGS

AF:

0.635

AC:

2206

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

(source)

DANN

Benign

0.35

PhyloP100

-1.7

PromoterAI

0.0024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over