rs616444

Positions:

• chr18-44905559-A-C
• chr18-44905559-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+36276A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 143,912 control chromosomes in the GnomAD database, including 517 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 0.077 (517 hom., cov: 32)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3	c.540+36276A>C		intron_variant		ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2	c.540+36276A>C		intron_variant			NM_015559.3	ENSP00000497406	P2

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11139 AN: 143792 Hom.: 516 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0176

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.0906

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0745

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

GnomAD4 genome AF: 0.0775 AC: 11150 AN: 143912 Hom.: 517 Cov.: 32 AF XY: 0.0773 AC XY: 5430 AN XY: 70282

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0792

Alfa AF: 0.0954 Hom.: 1087

Bravo AF: 0.0665

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.49

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: rs616444; hg19: chr18-42485524;