rs10789505

Variant names:

• chr1-47281006-G-C
• rs10789505
• NM_001048166.1:c.1452C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-47281006-G-C
• chr1-47281006-G-T
• chr1-47281006-G-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001048166.1(STIL):​c.1452C>G​(p.Ser484Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,613,872 control chromosomes in the GnomAD database, including 13,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S484S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.16 (3186 hom., cov: 32)
  • Exomes 𝑓: 0.098 (10113 hom.)
• Consequence: STIL NM_001048166.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.184
• Publications: 17 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: Orphanet, ClinGen
• microcephaly 7, primary, autosomal recessive

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.114).
• BP6: Variant 1-47281006-G-C is Benign according to our data. Variant chr1-47281006-G-C is described in ClinVar as Benign. ClinVar VariationId is 160051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.184 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 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.1452C>G	p.Ser484Ser	synonymous	Exon 12 of 17	NP_001041631.1	Q15468-2
	STIL	NM_001282936.1		c.1452C>G	p.Ser484Ser	synonymous	Exon 13 of 18	NP_001269865.1	Q15468-1
	STIL	NM_003035.2		c.1452C>G	p.Ser484Ser	synonymous	Exon 12 of 17	NP_003026.2	Q15468-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIL	ENST00000371877.8	TSL:1 MANE Select	c.1452C>G	p.Ser484Ser	synonymous	Exon 12 of 17	ENSP00000360944.3	Q15468-2
	STIL	ENST00000360380.7	TSL:1	c.1452C>G	p.Ser484Ser	synonymous	Exon 13 of 18	ENSP00000353544.3	Q15468-1
	STIL	ENST00000396221.6	TSL:1	c.1452C>G	p.Ser484Ser	synonymous	Exon 12 of 17	ENSP00000379523.2	E9PSF2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24761 AN: 151954 Hom.: 3186 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.120 AC: 30058 AN: 251294 AF XY: 0.118

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.0498

Gnomad ASJ exome AF: 0.0883

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.0533

Gnomad NFE exome AF: 0.0793

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0980 AC: 143303 AN: 1461800 Hom.: 10113 Cov.: 33 AF XY: 0.0998 AC XY: 72566 AN XY: 727190

African (AFR) AF: 0.364 AC: 12175 AN: 33474

American (AMR) AF: 0.0549 AC: 2454 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 2374 AN: 26136

East Asian (EAS) AF: 0.337 AC: 13391 AN: 39698

South Asian (SAS) AF: 0.171 AC: 14760 AN: 86242

European-Finnish (FIN) AF: 0.0552 AC: 2947 AN: 53410

Middle Eastern (MID) AF: 0.101 AC: 583 AN: 5768

European-Non Finnish (NFE) AF: 0.0789 AC: 87722 AN: 1111962

Other (OTH) AF: 0.114 AC: 6897 AN: 60394

GnomAD4 genome AF: 0.163 AC: 24784 AN: 152072 Hom.: 3186 Cov.: 32 AF XY: 0.163 AC XY: 12149 AN XY: 74310

African (AFR) AF: 0.350 AC: 14487 AN: 41432

American (AMR) AF: 0.0907 AC: 1385 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1569 AN: 5158

South Asian (SAS) AF: 0.176 AC: 849 AN: 4816

European-Finnish (FIN) AF: 0.0530 AC: 562 AN: 10610

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5223 AN: 67996

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.0688 Hom.: 170

Bravo AF: 0.175

Asia WGS AF: 0.222 AC: 773 AN: 3478

EpiCase AF: 0.0804

EpiControl AF: 0.0819

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	2	Microcephaly 7, primary, autosomal recessive (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.60
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs10789505; hg19: chr1-47746678; COSMIC: COSV54548036;