chr18-45057825-C-T

Position:

• chr18-45057825-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015559.3(SETBP1):​c.4172-5254C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,286 control chromosomes in the GnomAD database, including 1,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1194 hom., cov: 33)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETBP1	NM_015559.3	c.4172-5254C>T		intron_variant		ENST00000649279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETBP1	ENST00000649279.2	c.4172-5254C>T		intron_variant			NM_015559.3	P2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16895 AN: 152168 Hom.: 1192 Cov.: 33

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00750

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16895 AN: 152286 Hom.: 1194 Cov.: 33 AF XY: 0.110 AC XY: 8177 AN XY: 74460

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.00751

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.124

Alfa AF: 0.140 Hom.: 2230

Bravo AF: 0.0995

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.54

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: rs1868755; hg19: chr18-42637790;