rs11577960

chr1-47283180-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001048166.1(STIL):c.1134-721C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,044 control chromosomes in the GnomAD database, including 5,207 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 0.25 (5207 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STIL NM_001048166.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877

Genes affected

STIL (HGNC:10879): (STIL centriolar assembly protein) This gene encodes a cytoplasmic protein implicated in regulation of the mitotic spindle checkpoint, a regulatory pathway that monitors chromosome segregation during cell division to ensure the proper distribution of chromosomes to daughter cells. The protein is phosphorylated in mitosis and in response to activation of the spindle checkpoint, and disappears when cells transition to G1 phase. It interacts with a mitotic regulator, and its expression is required to efficiently activate the spindle checkpoint. It is proposed to regulate Cdc2 kinase activity during spindle checkpoint arrest. Chromosomal deletions that fuse this gene and the adjacent locus commonly occur in T cell leukemias, and are thought to arise through illegitimate V-(D)-J recombination events. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIL	NM_001048166.1	c.1134-721C>G		intron_variant		ENST00000371877.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIL	ENST00000371877.8	c.1134-721C>G		intron_variant		1	NM_001048166.1	P5

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38429 AN: 151926 Hom.: 5204 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0253

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.270

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.253 AC: 38436 AN: 152044 Hom.: 5207 Cov.: 32 AF XY: 0.247 AC XY: 18362 AN XY: 74324

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.269

Alfa AF: 0.276 Hom.: 753

Bravo AF: 0.248

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
Dann	Benign	0.68

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: rs11577960; hg19: chr1-47748852;