dbSNP rs5030168: WT1:c.785-20G>T (chr11-32428078-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024426.6(WT1):c.785-20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,582,834 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 21 hom. )

Consequence

WT1
NM_024426.6 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.904

Publications

2 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=-0.79).

BP6

Variant 11-32428078-C-A is Benign according to our data. Variant chr11-32428078-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0061 (930/152346) while in subpopulation AFR AF = 0.0212 (883/41580). AF 95% confidence interval is 0.0201. There are 9 homozygotes in GnomAd4. There are 447 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 930 AD gene.

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.785-20G>T	intron	N/A	NP_077744.4
WT1	NM_024424.5		c.785-20G>T	intron	N/A	NP_077742.3	H0Y7K5
WT1	NM_001407044.1		c.785-20G>T	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.785-20G>T	intron	N/A	ENSP00000415516.5	P19544-7
WT1	ENST00000639563.4	TSL:1	c.785-20G>T	intron	N/A	ENSP00000492269.3	P19544-8
WT1	ENST00000332351.9	TSL:1	c.785-20G>T	intron	N/A	ENSP00000331327.5	J3KNN9

Frequencies

GnomAD3 genomes

AF:

0.00612

AC:

931

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00166

AC:

362

AN:

218550

AF XY:

0.00125

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.000705

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000624

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000678

AC:

970

AN:

1430488

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

409

AN XY:

706706

show subpopulations

African (AFR)

AF:

0.0243

AC:

799

AN:

32906

American (AMR)

AF:

0.000859

AC:

AN:

41930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24852

East Asian (EAS)

AF:

0.00

AC:

AN:

38934

South Asian (SAS)

AF:

0.0000361

AC:

AN:

83196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51788

Middle Eastern (MID)

AF:

0.000934

AC:

AN:

5356

European-Non Finnish (NFE)

AF:

0.0000265

AC:

AN:

1092732

Other (OTH)

AF:

0.00167

AC:

AN:

58794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00610

AC:

930

AN:

152346

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0212

AC:

883

AN:

41580

American (AMR)

AF:

0.00209

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00540

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

11p partial monosomy syndrome;C0950121:Drash syndrome;C0950122:Frasier syndrome;CN033288:Wilms tumor 1 (1)

Drash syndrome (1)

Frasier syndrome (1)

Meacham syndrome (1)

Nephrotic syndrome, type 4 (1)

Wilms tumor 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.4

(source)

DANN

Benign

0.56

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism

(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