18-44950031-G-C

Variant names:

Variant summary

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

The NM_015559.3(SETBP1):c.691G>C(p.Val231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,614,022 control chromosomes in the GnomAD database, including 33,960 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2738 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31222 hom. )

Consequence

SETBP1
NM_015559.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0440

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=0.0025821924).

BP6

Variant 18-44950031-G-C is Benign according to our data. Variant chr18-44950031-G-C is described in ClinVar as [Benign]. Clinvar id is 159885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-44950031-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETBP1	NM_015559.3 link	c.691G>C	p.Val231Leu	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.691G>C	p.Val231Leu	missense_variant	Exon 4 of 6		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28410

AN:

152094

Hom.:

2739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.191

AC:

47951

AN:

250928

Hom.:

5025

AF XY:

0.197

AC XY:

26737

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0120

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.203

AC:

296307

AN:

1461810

Hom.:

31222

Cov.:

AF XY:

0.204

AC XY:

148357

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.187

AC:

28413

AN:

152212

Hom.:

2738

Cov.:

AF XY:

0.187

AC XY:

13919

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.0154

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.178

Hom.:

1659

Bravo

AF:

0.182

TwinsUK

AF:

0.207

AC:

769

ALSPAC

AF:

0.199

AC:

766

ESP6500AA

AF:

0.148

AC:

652

ESP6500EA

AF:

0.204

AC:

1758

ExAC

AF:

0.193

AC:

23408

Asia WGS

AF:

0.148

AC:

518

AN:

3478

EpiCase

AF:

0.212

EpiControl

AF:

0.212

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

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

- -

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 29% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 27. Only high quality variants are reported. -

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

0.079

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.3

DANN

Benign

0.77

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.82

.;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.88

.;N

REVEL

Benign

0.036

Sift

Uncertain

0.029

.;D

Sift4G

Benign

0.45

.;T

Polyphen

0.0060

B;B

Vest4

0.027

MPC

0.25

ClinPred

0.0025

GERP RS

-5.5

Varity_R

0.076

gMVP

0.13

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