rs1064204

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1130I) has been classified as Uncertain significance.

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

Publications

32 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

SETBP1 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 (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 VariationId 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 rank	MANE	Protein	UniProt
SETBP1	NM_015559.3 link	c.3388C>A	p.Pro1130Thr	missense_variant	Exon 4 of 6	ENST00000649279.2	NP_056374.2	Q9Y6X0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2 link	c.3388C>A	p.Pro1130Thr	missense_variant	Exon 4 of 6		NM_015559.3	ENSP00000497406.1		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

GnomAD2 exomes

AF:

0.138

AC:

34749

AN:

251312

AF XY:

0.133

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 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

African (AFR)

AF:

0.0359

AC:

1202

AN:

33480

American (AMR)

AF:

0.301

AC:

13459

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3115

AN:

26136

East Asian (EAS)

AF:

0.191

AC:

7568

AN:

39696

South Asian (SAS)

AF:

0.121

AC:

10424

AN:

86258

European-Finnish (FIN)

AF:

0.0739

AC:

3949

AN:

53420

Middle Eastern (MID)

AF:

0.133

AC:

765

AN:

5768

European-Non Finnish (NFE)

AF:

0.114

AC:

126566

AN:

1111988

Other (OTH)

AF:

0.118

AC:

7131

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

10346

20692

31037

41383

51729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4772

9544

14316

19088

23860

<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:

0.103

AC:

15687

AN:

152114

Hom.:

1041

Cov.:

AF XY:

0.105

AC XY:

7829

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0402

AC:

1670

AN:

41528

American (AMR)

AF:

0.214

AC:

3266

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

388

AN:

3466

East Asian (EAS)

AF:

0.183

AC:

944

AN:

5158

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4800

European-Finnish (FIN)

AF:

0.0825

AC:

874

AN:

10590

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7604

AN:

68002

Other (OTH)

AF:

0.118

AC:

249

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

700

1400

2101

2801

3501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.114

Hom.:

4365

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Schinzel-Giedion syndrome

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

2.0

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

Mutation Taster

=99/1

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over