1-47260415-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001048166.1(STIL):c.2954A>G(p.His985Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,613,810 control chromosomes in the GnomAD database, including 71,390 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5206 hom., cov: 32)

Exomes 𝑓: 0.29 ( 66184 hom. )

Consequence

STIL
NM_001048166.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0110

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00568372).

BP6

Variant 1-47260415-T-C is Benign according to our data. Variant chr1-47260415-T-C is described in ClinVar as [Benign]. Clinvar id is 94094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-47260415-T-C is described in Lovd as [Benign].

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 rank	MANE	Protein	UniProt
STIL	NM_001048166.1 link	c.2954A>G	p.His985Arg	missense_variant	Exon 16 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.2954A>G	p.His985Arg	missense_variant	Exon 16 of 17	1	NM_001048166.1	ENSP00000360944.3		Q15468-2

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38426

AN:

152010

Hom.:

5203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.239

AC:

59984

AN:

251460

Hom.:

8127

AF XY:

0.246

AC XY:

33418

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.0230

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.293

AC:

428455

AN:

1461682

Hom.:

66184

Cov.:

AF XY:

0.292

AC XY:

212198

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.253

AC:

38433

AN:

152128

Hom.:

5206

Cov.:

AF XY:

0.247

AC XY:

18371

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.0254

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.295

Hom.:

16970

Bravo

AF:

0.248

TwinsUK

AF:

0.319

AC:

1183

ALSPAC

AF:

0.321

AC:

1237

ESP6500AA

AF:

0.219

AC:

966

ESP6500EA

AF:

0.315

AC:

2710

ExAC

AF:

0.242

AC:

29387

Asia WGS

AF:

0.134

AC:

470

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jul 24, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 03, 2013

Eurofins Ntd Llc (ga)

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

- -

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

- -

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Microcephaly 7, primary, autosomal recessive

Benign:2

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.2

DANN

Benign

0.47

DEOGEN2

Benign

0.10

T;.;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.47

T;T;T;T

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

L;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Benign

0.030

Sift

Benign

0.31

T;.;T;T

Sift4G

Benign

0.61

T;T;T;T

Polyphen

0.0010

B;.;B;B

Vest4

0.043

MPC

0.13

ClinPred

0.0062

GERP RS

0.31

Varity_R

0.027

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over