rs574196735

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015559.3(SETBP1):c.4554G>A(p.Glu1518Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000583 in 1,473,276 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00075 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00056 ( 5 hom. )

Consequence

SETBP1
NM_015559.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 3.80

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 18-45063461-G-A is Benign according to our data. Variant chr18-45063461-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 159881.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=1}. Variant chr18-45063461-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000746 (113/151568) while in subpopulation AMR AF= 0.00105 (16/15244). AF 95% confidence interval is 0.000658. There are 1 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETBP1	NM_015559.3 link	c.4554G>A	p.Glu1518Glu	synonymous_variant	Exon 6 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.4554G>A	p.Glu1518Glu	synonymous_variant	Exon 6 of 6		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.000746

AC:

113

AN:

151460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.000457

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00122

AC:

AN:

73190

Hom.:

AF XY:

0.00112

AC XY:

AN XY:

37406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000779

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.000564

AC:

746

AN:

1321708

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

381

AN XY:

645256

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.0152

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000168

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000221

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.000746

AC:

113

AN:

151568

Hom.:

Cov.:

AF XY:

0.000810

AC XY:

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000419

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000457

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:5

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SETBP1: BP4, BS1 -

Schinzel-Giedion syndrome

Uncertain:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent, not in splice site, no coverage in ExAC, 1 report as a VUS for Schinzel-Giedion syndrome in ClinVar (Uchicago, no additional info) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.0

DANN

Benign

0.62

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