18-44905559-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015559.3(SETBP1):​c.540+36276A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 143,912 control chromosomes in the GnomAD database, including 517 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 0.077 ( 517 hom., cov: 32)

Consequence

SETBP1
NM_015559.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.595
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SETBP1NM_015559.3 linkuse as main transcriptc.540+36276A>C intron_variant ENST00000649279.2 NP_056374.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SETBP1ENST00000649279.2 linkuse as main transcriptc.540+36276A>C intron_variant NM_015559.3 ENSP00000497406 P2Q9Y6X0-1

Frequencies

GnomAD3 genomes
AF:
0.0775
AC:
11139
AN:
143792
Hom.:
516
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0213
Gnomad AMI
AF:
0.0956
Gnomad AMR
AF:
0.0534
Gnomad ASJ
AF:
0.140
Gnomad EAS
AF:
0.0176
Gnomad SAS
AF:
0.125
Gnomad FIN
AF:
0.0935
Gnomad MID
AF:
0.0906
Gnomad NFE
AF:
0.111
Gnomad OTH
AF:
0.0745
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0775
AC:
11150
AN:
143912
Hom.:
517
Cov.:
32
AF XY:
0.0773
AC XY:
5430
AN XY:
70282
show subpopulations
Gnomad4 AFR
AF:
0.0212
Gnomad4 AMR
AF:
0.0533
Gnomad4 ASJ
AF:
0.140
Gnomad4 EAS
AF:
0.0176
Gnomad4 SAS
AF:
0.125
Gnomad4 FIN
AF:
0.0935
Gnomad4 NFE
AF:
0.111
Gnomad4 OTH
AF:
0.0792
Alfa
AF:
0.0954
Hom.:
1087
Bravo
AF:
0.0665
Asia WGS
AF:
0.0750
AC:
263
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.4
DANN
Benign
0.49

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: rs616444; hg19: chr18-42485524; API