18-44701183-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_015559.3(SETBP1):c.-164C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 630,186 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: SETBP1 NM_015559.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.438

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=-0.37).
• BP6: Variant 18-44701183-C-G is Benign according to our data. Variant chr18-44701183-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2578809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00137 (208/152292) while in subpopulation AMR AF= 0.00274 (42/15304). AF 95% confidence interval is 0.00209. There are 1 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETBP1	NM_015559.3	c.-164C>G		5_prime_UTR_variant	2/6	ENST00000649279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETBP1	ENST00000649279.2	c.-164C>G		5_prime_UTR_variant	2/6		NM_015559.3	P2

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 209 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00164 AC: 785 AN: 477894 Hom.: 2 Cov.: 7 AF XY: 0.00172 AC XY: 414 AN XY: 241320

Gnomad4 AFR exome AF: 0.000993

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000570

Gnomad4 FIN exome AF: 0.0000321

Gnomad4 NFE exome AF: 0.000988

Gnomad4 OTH exome AF: 0.00351

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152292 Hom.: 1 Cov.: 32 AF XY: 0.00136 AC XY: 101 AN XY: 74456

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00201 Hom.: 1

Bravo AF: 0.00161

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

SETBP1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	17
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs145284354; hg19: chr18-42281148;