rs139896661

Positions:

• chr18-45063197-G-A
• chr18-45063197-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015559.3(SETBP1):​c.4290G>A​(p.Val1430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,613,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V1430V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00044 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: SETBP1 NM_015559.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.372

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 18-45063197-G-A is Benign according to our data. Variant chr18-45063197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 159879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.372 with no splicing effect.
• BS2: High AC in GnomAd4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETBP1	NM_015559.3	c.4290G>A	p.Val1430=	synonymous_variant	6/6	ENST00000649279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETBP1	ENST00000649279.2	c.4290G>A	p.Val1430=	synonymous_variant	6/6		NM_015559.3	P2

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 67 AN: 151960 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000593 AC: 149 AN: 251306 Hom.: 0 AF XY: 0.000589 AC XY: 80 AN XY: 135890

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00360

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000386 AC: 564 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.000364 AC XY: 265 AN XY: 727238

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00307

Gnomad4 NFE exome AF: 0.000337

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000441 AC: 67 AN: 151960 Hom.: 1 Cov.: 32 AF XY: 0.000620 AC XY: 46 AN XY: 74210

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000441 Hom.: 0

Bravo AF: 0.000151

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 15, 2014

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 07, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.0
DANN	Benign	0.70

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: rs139896661; hg19: chr18-42643162;