NM_015559.3:c.540+3799A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015559.3(SETBP1):​c.540+3799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,104 control chromosomes in the GnomAD database, including 22,955 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 0.55 ( 22955 hom., cov: 33)

Consequence

SETBP1
NM_015559.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

Publications

11 publications found
Variant links:
Genes affected
SETBP1 (HGNC:15573): (SET binding protein 1) This gene encodes a protein which contains a several motifs including a ski homology region and a SET-binding region in addition to three nuclear localization signals. The encoded protein has been shown to bind the SET nuclear oncogene which is involved in DNA replication. Mutations in this gene are associated with Schinzel-Giedion midface retraction syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
SETBP1 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • intellectual disability, autosomal dominant 29
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • Schinzel-Giedion syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • intellectual disability-expressive aphasia-facial dysmorphism syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETBP1NM_015559.3 linkc.540+3799A>G intron_variant Intron 3 of 5 ENST00000649279.2 NP_056374.2 Q9Y6X0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETBP1ENST00000649279.2 linkc.540+3799A>G intron_variant Intron 3 of 5 NM_015559.3 ENSP00000497406.1 Q9Y6X0-1

Frequencies

GnomAD3 genomes
AF:
0.548
AC:
83313
AN:
151986
Hom.:
22932
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.551
Gnomad AMI
AF:
0.655
Gnomad AMR
AF:
0.502
Gnomad ASJ
AF:
0.585
Gnomad EAS
AF:
0.482
Gnomad SAS
AF:
0.421
Gnomad FIN
AF:
0.597
Gnomad MID
AF:
0.544
Gnomad NFE
AF:
0.561
Gnomad OTH
AF:
0.522
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.548
AC:
83395
AN:
152104
Hom.:
22955
Cov.:
33
AF XY:
0.547
AC XY:
40641
AN XY:
74362
show subpopulations
African (AFR)
AF:
0.551
AC:
22861
AN:
41480
American (AMR)
AF:
0.502
AC:
7679
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.585
AC:
2030
AN:
3468
East Asian (EAS)
AF:
0.482
AC:
2491
AN:
5172
South Asian (SAS)
AF:
0.422
AC:
2032
AN:
4816
European-Finnish (FIN)
AF:
0.597
AC:
6320
AN:
10580
Middle Eastern (MID)
AF:
0.537
AC:
158
AN:
294
European-Non Finnish (NFE)
AF:
0.561
AC:
38117
AN:
67988
Other (OTH)
AF:
0.528
AC:
1112
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1962
3924
5887
7849
9811
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
712
1424
2136
2848
3560
<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:
0.553
Hom.:
74654
Bravo
AF:
0.545
Asia WGS
AF:
0.492
AC:
1715
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.68
DANN
Benign
0.61
PhyloP100
-0.23
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

Publications

Other links and lift over

dbSNP: rs617459; hg19: chr18-42453047; API