rs7228266

Positions:

• chr18-45040568-G-A

Variant summary

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

The NM_015559.3(SETBP1):​c.4171+1913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,048 control chromosomes in the GnomAD database, including 6,880 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 0.30 (6880 hom., cov: 32)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3	c.4171+1913G>A		intron_variant		ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2	c.4171+1913G>A		intron_variant			NM_015559.3	ENSP00000497406	P2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45396 AN: 151930 Hom.: 6880 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.299 AC: 45411 AN: 152048 Hom.: 6880 Cov.: 32 AF XY: 0.294 AC XY: 21882 AN XY: 74342

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.308

Alfa AF: 0.326 Hom.: 16455

Bravo AF: 0.306

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
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: rs7228266; hg19: chr18-42620533;