1-47281006-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.184

Publications

16 publications found

Variant links:

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

STIL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIL	NM_001048166.1 link	c.1452C>G	p.Ser484Ser	synonymous_variant	Exon 12 of 17	ENST00000371877.8	NP_001041631.1	Q15468-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIL	ENST00000371877.8 link	c.1452C>G	p.Ser484Ser	synonymous_variant	Exon 12 of 17	1	NM_001048166.1	ENSP00000360944.3		Q15468-2

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24761

AN:

151954

Hom.:

3186

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0998

AC XY:

72566

AN XY:

727190

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

7569

15137

22706

30274

37843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3598

7196

10794

14392

17990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24784

AN:

152072

Hom.:

3186

Cov.:

AF XY:

0.163

AC XY:

12149

AN XY:

74310

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0768

AC:

5223

AN:

67996

Other (OTH)

AF:

0.124

AC:

262

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

919

1837

2756

3674

4593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microcephaly 7, primary, autosomal recessive

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.5

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over