Variant chr18-44953350-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 (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 id 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/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3 linkuse as main transcript	c.4000+10T>A		intron_variant		ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2 linkuse as main transcript	c.4000+10T>A		intron_variant			NM_015559.3	ENSP00000497406	P2	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

GnomAD3 exomes

AF:

0.139

AC:

34156

AN:

245482

Hom.:

3281

AF XY:

0.134

AC XY:

17799

AN XY:

133144

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 SAS exome

AF:

0.120

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

Gnomad4 AFR exome

AF:

0.0373

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.119

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0745

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.104

AC:

15795

AN:

152194

Hom.:

1047

Cov.:

AF XY:

0.106

AC XY:

7886

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0835

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.118

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	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. -

Schinzel-Giedion syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.65

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