rs617459

Positions:

• chr18-44873082-A-G
• chr18-44873082-A-T

Variant summary

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

The NM_015559.3(SETBP1):​c.540+3799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,104 control chromosomes in the GnomAD database, including 22,955 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 0.55 (22955 hom., cov: 33)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETBP1	NM_015559.3	c.540+3799A>G		intron_variant		ENST00000649279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETBP1	ENST00000649279.2	c.540+3799A>G		intron_variant			NM_015559.3	P2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83313 AN: 151986 Hom.: 22932 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.548 AC: 83395 AN: 152104 Hom.: 22955 Cov.: 33 AF XY: 0.547 AC XY: 40641 AN XY: 74362

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.528

Alfa AF: 0.554 Hom.: 48186

Bravo AF: 0.545

Asia WGS AF: 0.492 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.61

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: rs617459; hg19: chr18-42453047;