chr11-32387819-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_024426.6(WT1):​c.*1239T>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00212 in 233,246 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 1 hom. )

Consequence

WT1
NM_024426.6 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 3.71
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 11-32387819-A-T is Benign according to our data. Variant chr11-32387819-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 304370.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00181 (275/152320) while in subpopulation AMR AF= 0.00425 (65/15302). AF 95% confidence interval is 0.00342. There are 4 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 275 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WT1NM_024426.6 linkuse as main transcriptc.*1239T>A 3_prime_UTR_variant 10/10 ENST00000452863.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WT1ENST00000452863.10 linkuse as main transcriptc.*1239T>A 3_prime_UTR_variant 10/101 NM_024426.6 P19544-7

Frequencies

GnomAD3 genomes
AF:
0.00180
AC:
274
AN:
152202
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000748
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.0138
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.00134
Gnomad OTH
AF:
0.00527
GnomAD4 exome
AF:
0.00271
AC:
219
AN:
80926
Hom.:
1
Cov.:
0
AF XY:
0.00301
AC XY:
112
AN XY:
37196
show subpopulations
Gnomad4 AFR exome
AF:
0.00103
Gnomad4 AMR exome
AF:
0.00721
Gnomad4 ASJ exome
AF:
0.0109
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00222
Gnomad4 OTH exome
AF:
0.00325
GnomAD4 genome
AF:
0.00181
AC:
275
AN:
152320
Hom.:
4
Cov.:
32
AF XY:
0.00160
AC XY:
119
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000746
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.0138
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00134
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00194
Hom.:
0
Bravo
AF:
0.00232
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Meacham syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Nephrotic syndrome, type 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Wilms tumor 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
16
DANN
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs534396876; hg19: chr11-32409365; API