18-44680946-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015559.3(SETBP1):c.-248G>T variant causes a 5 prime UTR 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.914

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]

ACMG classification

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 GnomAd at 937 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETBP1	NM_015559.3	c.-248G>T		5_prime_UTR_variant	1/6	ENST00000649279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETBP1	ENST00000649279.2	c.-248G>T		5_prime_UTR_variant	1/6		NM_015559.3	P2
SETBP1	ENST00000426838.8	c.-173+551G>T		intron_variant		1		A2
SETBP1	ENST00000677699.1	c.-248G>T		5_prime_UTR_variant	1/5			A2
SETBP1	ENST00000677068.1	c.-173+551G>T		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.00621 AC: 937 AN: 150894 Hom.: 4 Cov.: 31

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: 0 AN: 66 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 46

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.: 4 Cov.: 31 AF XY: 0.00584 AC XY: 431 AN XY: 73744

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.: 1

Bravo AF: 0.00589

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs563748893; hg19: chr18-42260911; COSMIC: COSV56330220; COSMIC: COSV56330220;