18-44701044-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015559.3(SETBP1):c.-172-130del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 287,316 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (18 hom., cov: 32)
  • Exomes 𝑓: 0.015 (20 hom.)
• Consequence: SETBP1 NM_015559.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589

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 -10 ACMG points.

• BP6: Variant 18-44701044-TA-T is Benign according to our data. Variant chr18-44701044-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2023/152300) while in subpopulation NFE AF= 0.0192 (1303/68022). AF 95% confidence interval is 0.0183. There are 18 homozygotes in gnomad4. There are 1041 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2023 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETBP1	NM_015559.3	c.-172-130del		intron_variant		ENST00000649279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETBP1	ENST00000649279.2	c.-172-130del		intron_variant			NM_015559.3	P2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2023 AN: 152182 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.0147 AC: 1986 AN: 135016 Hom.: 20 AF XY: 0.0148 AC XY: 1008 AN XY: 68076

Gnomad4 AFR exome AF: 0.00305

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.00869

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00758

Gnomad4 FIN exome AF: 0.0253

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0133 AC: 2023 AN: 152300 Hom.: 18 Cov.: 32 AF XY: 0.0140 AC XY: 1041 AN XY: 74482

Gnomad4 AFR AF: 0.00358

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0192

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00802 Hom.: 3

Bravo AF: 0.0108

Asia WGS AF: 0.00231 AC: 8 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

GeneDx

Aug 14, 2018

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Computational scores

Source: dbNSFP v4.3

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: rs200931857; hg19: chr18-42281009;