chr18-44953350-T-A

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.4000+10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,609,664 control chromosomes in the GnomAD database, including 12,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1047 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11890 hom. )

Consequence

SETBP1
NM_015559.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.586

Publications

12 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 (BayesDel_noAF=-0.74).

BP6

Variant 18-44953350-T-A is Benign according to our data. Variant chr18-44953350-T-A is described in ClinVar as Benign. ClinVar VariationId is 159877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETBP1	NM_015559.3 link	c.4000+10T>A		intron_variant	Intron 4 of 5	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.4000+10T>A		intron_variant	Intron 4 of 5		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15757

AN:

152076

Hom.:

1034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0835

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.114

GnomAD2 exomes

AF:

0.139

AC:

34156

AN:

245482

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.0384

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.0770

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.120

AC:

174169

AN:

1457470

Hom.:

11890

Cov.:

AF XY:

0.119

AC XY:

86625

AN XY:

725188

show subpopulations

African (AFR)

AF:

0.0373

AC:

1247

AN:

33416

American (AMR)

AF:

0.301

AC:

13408

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3113

AN:

26112

East Asian (EAS)

AF:

0.191

AC:

7567

AN:

39676

South Asian (SAS)

AF:

0.121

AC:

10441

AN:

86042

European-Finnish (FIN)

AF:

0.0745

AC:

3932

AN:

52806

Middle Eastern (MID)

AF:

0.133

AC:

765

AN:

5764

European-Non Finnish (NFE)

AF:

0.114

AC:

126562

AN:

1108892

Other (OTH)

AF:

0.118

AC:

7134

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

7580

15159

22739

30318

37898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4766

9532

14298

19064

23830

<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:

0.104

AC:

15795

AN:

152194

Hom.:

1047

Cov.:

AF XY:

0.106

AC XY:

7886

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0418

AC:

1738

AN:

41554

American (AMR)

AF:

0.215

AC:

3281

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

391

AN:

3472

East Asian (EAS)

AF:

0.181

AC:

933

AN:

5154

South Asian (SAS)

AF:

0.114

AC:

552

AN:

4824

European-Finnish (FIN)

AF:

0.0835

AC:

885

AN:

10604

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7621

AN:

67984

Other (OTH)

AF:

0.118

AC:

250

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

695

1390

2085

2780

3475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0706

Hom.:

102

Bravo

AF:

0.114

Asia WGS

AF:

0.182

AC:

634

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 07, 2018

Athena Diagnostics

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

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

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 45% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 42. Only high quality variants are reported. -

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

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

-0.59

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