chr18-44952728-C-A

Position:

chr18-44952728-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015559.3(SETBP1):c.3388C>A(p.Pro1130Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,613,980 control chromosomes in the GnomAD database, including 12,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 1041 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11889 hom. )

Consequence

SETBP1
NM_015559.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.01

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017183125).

BP6

Variant 18-44952728-C-A is Benign according to our data. Variant chr18-44952728-C-A is described in ClinVar as [Benign]. Clinvar id is 159873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3 linkuse as main transcript	c.3388C>A	p.Pro1130Thr	missense_variant	4/6	ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2 linkuse as main transcript	c.3388C>A	p.Pro1130Thr	missense_variant	4/6		NM_015559.3	ENSP00000497406	P2	Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15650

AN:

151996

Hom.:

1028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0402

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0825

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.138

AC:

34749

AN:

251312

Hom.:

3374

AF XY:

0.133

AC XY:

18062

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.0762

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.119

AC:

174179

AN:

1461866

Hom.:

11889

Cov.:

AF XY:

0.119

AC XY:

86575

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0739

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.103

AC:

15687

AN:

152114

Hom.:

1041

Cov.:

AF XY:

0.105

AC XY:

7829

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0402

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0825

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.116

Hom.:

2825

Bravo

AF:

0.113

TwinsUK

AF:

0.112

AC:

414

ALSPAC

AF:

0.111

AC:

427

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.120

AC:

1030

ExAC

AF:

0.129

AC:

15657

Asia WGS

AF:

0.181

AC:

629

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.116

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

Benign, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 43. Only high quality variants are reported. -

Schinzel-Giedion syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.093

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

.;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.59

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.049

Sift

Benign

0.10

.;T

Sift4G

Benign

0.079

.;T

Polyphen

0.0

B;B

Vest4

0.054

MPC

0.32

ClinPred

0.0095

GERP RS

4.1

Varity_R

0.088

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over