rs3744825

Variant names:

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.3301G>A(p.Val1101Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,728 control chromosomes in the GnomAD database, including 14,285 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 (★★).

Frequency

Genomes: 𝑓 0.11 ( 1124 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13161 hom. )

Consequence

SETBP1
NM_015559.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.23

Publications

41 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=0.004114777).

BP6

Variant 18-44952641-G-A is Benign according to our data. Variant chr18-44952641-G-A is described in ClinVar as Benign. ClinVar VariationId is 159872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETBP1	NM_015559.3 link	c.3301G>A	p.Val1101Ile	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.3301G>A	p.Val1101Ile	missense_variant	Exon 4 of 6		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16311

AN:

151918

Hom.:

1125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.0864

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.0949

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.123

AC:

30826

AN:

250638

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.0822

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.129

AC:

187844

AN:

1461690

Hom.:

13161

Cov.:

AF XY:

0.127

AC XY:

92524

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.0479

AC:

1603

AN:

33478

American (AMR)

AF:

0.0824

AC:

3684

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3649

AN:

26132

East Asian (EAS)

AF:

0.310

AC:

12320

AN:

39694

South Asian (SAS)

AF:

0.0836

AC:

7210

AN:

86256

European-Finnish (FIN)

AF:

0.135

AC:

7197

AN:

53420

Middle Eastern (MID)

AF:

0.0969

AC:

559

AN:

5766

European-Non Finnish (NFE)

AF:

0.129

AC:

143717

AN:

1111834

Other (OTH)

AF:

0.131

AC:

7905

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10276

20553

30829

41106

51382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5262

10524

15786

21048

26310

<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:

0.107

AC:

16305

AN:

152038

Hom.:

1124

Cov.:

AF XY:

0.108

AC XY:

8006

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0503

AC:

2087

AN:

41500

American (AMR)

AF:

0.0862

AC:

1317

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

475

AN:

3470

East Asian (EAS)

AF:

0.280

AC:

1443

AN:

5150

South Asian (SAS)

AF:

0.0950

AC:

457

AN:

4812

European-Finnish (FIN)

AF:

0.142

AC:

1494

AN:

10544

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8525

AN:

67980

Other (OTH)

AF:

0.120

AC:

252

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

714

1428

2143

2857

3571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.122

Hom.:

4218

Bravo

AF:

0.104

TwinsUK

AF:

0.127

AC:

470

ALSPAC

AF:

0.139

AC:

536

ESP6500AA

AF:

0.0572

AC:

252

ESP6500EA

AF:

0.125

AC:

1072

ExAC

AF:

0.121

AC:

14714

Asia WGS

AF:

0.176

AC:

610

AN:

3478

EpiCase

AF:

0.127

EpiControl

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

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

0.074

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.71

.;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PhyloP100

1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

0.39

.;N

REVEL

Benign

0.033

Sift

Benign

0.14

.;T

Sift4G

Benign

0.22

.;T

Polyphen

0.052

B;B

Vest4

0.095

MPC

0.22

ClinPred

0.0021

GERP RS

-0.53

Varity_R

0.027

gMVP

0.083

Mutation Taster

=100/0

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