NM_001048166.1:c.1134-721C>G

Variant names:

• chr1-47283180-G-C
• rs11577960
• NM_001048166.1:c.1134-721C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

STIL Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• microcephaly 7, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• holoprosencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048166.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIL	NM_001048166.1	MANE Select	c.1134-721C>G		intron	N/A	NP_001041631.1
	STIL	NM_001282936.1		c.1134-721C>G		intron	N/A	NP_001269865.1
	STIL	NM_003035.2		c.1134-721C>G		intron	N/A	NP_003026.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIL	ENST00000371877.8	TSL:1 MANE Select	c.1134-721C>G		intron	N/A	ENSP00000360944.3
	STIL	ENST00000360380.7	TSL:1	c.1134-721C>G		intron	N/A	ENSP00000353544.3
	STIL	ENST00000396221.6	TSL:1	c.1134-721C>G		intron	N/A	ENSP00000379523.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.202 AC: 8370 AN: 41478

American (AMR) AF: 0.214 AC: 3267 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3468

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5176

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4812

European-Finnish (FIN) AF: 0.245 AC: 2594 AN: 10576

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21320 AN: 67974

Other (OTH) AF: 0.269 AC: 566 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11577960; hg19: chr1-47748852;