dbSNP rs8091231: SETBP1:p.Ala390Ala (chr18-44950510-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015559.3(SETBP1):c.1170C>T(p.Ala390Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0008 in 1,614,062 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 6 hom. )

Consequence

SETBP1
NM_015559.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.64

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
Schinzel-Giedion syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Laboratory for Molecular Medicine, PanelApp Australia, G2P
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 18-44950510-C-T is Benign according to our data. Variant chr18-44950510-C-T is described in ClinVar as Benign. ClinVar VariationId is 159867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0043 (655/152260) while in subpopulation AFR AF = 0.0152 (631/41554). AF 95% confidence interval is 0.0142. There are 7 homozygotes in GnomAd4. There are 282 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 655 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETBP1	NM_015559.3	MANE Select	c.1170C>T	p.Ala390Ala	synonymous	Exon 4 of 6	NP_056374.2	Q9Y6X0-1
SETBP1	NM_001379141.1		c.1170C>T	p.Ala390Ala	synonymous	Exon 4 of 6	NP_001366070.1	Q9Y6X0-1
SETBP1	NM_001379142.1		c.1170C>T	p.Ala390Ala	synonymous	Exon 4 of 6	NP_001366071.1	Q9Y6X0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETBP1	ENST00000649279.2	MANE Select	c.1170C>T	p.Ala390Ala	synonymous	Exon 4 of 6	ENSP00000497406.1	Q9Y6X0-1
SETBP1	ENST00000677068.1		c.1170C>T	p.Ala390Ala	synonymous	Exon 4 of 6	ENSP00000504398.1	Q9Y6X0-1
SETBP1	ENST00000677077.1		c.1170C>T	p.Ala390Ala	synonymous	Exon 4 of 6	ENSP00000503656.1	Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

652

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00106

AC:

263

AN:

249074

AF XY:

0.000688

show subpopulations

Gnomad AFR exome

AF:

0.0155

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000435

AC:

636

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

300

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0163

AC:

546

AN:

33476

American (AMR)

AF:

0.000648

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1112000

Other (OTH)

AF:

0.000844

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00430

AC:

655

AN:

152260

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

282

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0152

AC:

631

AN:

41554

American (AMR)

AF:

0.00131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00222

Hom.:

Bravo

AF:

0.00496

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (1)

Schinzel-Giedion syndrome (1)

SETBP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

(source)

DANN

Benign

0.43

PhyloP100

-1.6

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over