chr18-45032126-C-T

Position:

• chr18-45032126-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.4001-6359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,922 control chromosomes in the GnomAD database, including 9,652 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 0.35 (9652 hom., cov: 32)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETBP1	NM_015559.3	c.4001-6359C>T		intron_variant		ENST00000649279.2	NP_056374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETBP1	ENST00000649279.2	c.4001-6359C>T		intron_variant			NM_015559.3	ENSP00000497406	P2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52921 AN: 151804 Hom.: 9658 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.348 AC: 52921 AN: 151922 Hom.: 9652 Cov.: 32 AF XY: 0.348 AC XY: 25848 AN XY: 74206

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.363

Alfa AF: 0.396 Hom.: 24651

Bravo AF: 0.340

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.53

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: rs10502849; hg19: chr18-42612091;