rs2852779

Variant names:

• chr18-44712373-T-G
• rs2852779
• NM_015559.3:c.486+10541T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015559.3(SETBP1):​c.486+10541T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,050 control chromosomes in the GnomAD database, including 2,134 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 0.17 (2134 hom., cov: 31)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 3 publications found

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]

SETBP1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 29

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Schinzel-Giedion syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• intellectual disability-expressive aphasia-facial dysmorphism syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETBP1	NM_015559.3	c.486+10541T>G		intron_variant	Intron 2 of 5	ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2	c.486+10541T>G		intron_variant	Intron 2 of 5		NM_015559.3	ENSP00000497406.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25408 AN: 151928 Hom.: 2132 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.167 AC: 25420 AN: 152050 Hom.: 2134 Cov.: 31 AF XY: 0.165 AC XY: 12241 AN XY: 74332

African (AFR) AF: 0.193 AC: 8009 AN: 41458

American (AMR) AF: 0.177 AC: 2705 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3468

East Asian (EAS) AF: 0.145 AC: 749 AN: 5168

South Asian (SAS) AF: 0.0929 AC: 447 AN: 4814

European-Finnish (FIN) AF: 0.139 AC: 1468 AN: 10586

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10735 AN: 67974

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.160 Hom.: 1081

Bravo AF: 0.175

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-0.16
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2852779; hg19: chr18-42292338;