Variant 18-44680946-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015559.3(SETBP1):c.-248G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 151,012 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SETBP1
NM_015559.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.914

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 18-44680946-G-T is Benign according to our data. Variant chr18-44680946-G-T is described in ClinVar as [Benign]. Clinvar id is 2571012.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0062 (937/151012) while in subpopulation NFE AF= 0.0089 (602/67656). AF 95% confidence interval is 0.00831. There are 4 homozygotes in gnomad4. There are 431 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 937 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3 linkuse as main transcript	c.-248G>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	ENST00000649279.2	NP_056374.2	Q9Y6X0-1
SETBP1	NM_015559.3 linkuse as main transcript	c.-248G>T		5_prime_UTR_variant	1/6	ENST00000649279.2	NP_056374.2	Q9Y6X0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279 linkuse as main transcript	c.-248G>T		5_prime_UTR_premature_start_codon_gain_variant	1/6		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1
SETBP1	ENST00000649279 linkuse as main transcript	c.-248G>T		5_prime_UTR_variant	1/6		NM_015559.3	ENSP00000497406.1		Q9Y6X0-1

Frequencies

GnomAD3 genomes

AF:

0.00621

AC:

937

AN:

150894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00751

Gnomad ASJ

AF:

0.00376

Gnomad EAS

AF:

0.00310

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00949

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00890

Gnomad OTH

AF:

0.00965

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00620

AC:

937

AN:

151012

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

431

AN XY:

73744

show subpopulations

Gnomad4 AFR

AF:

0.00158

Gnomad4 AMR

AF:

0.00750

Gnomad4 ASJ

AF:

0.00376

Gnomad4 EAS

AF:

0.00311

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00949

Gnomad4 NFE

AF:

0.00890

Gnomad4 OTH

AF:

0.00955

Alfa

AF:

0.00721

Hom.:

Bravo

AF:

0.00589

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

SETBP1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.5

DANN

Benign

0.82

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