rs146387723

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001048166.1(STIL):c.3786G>A(p.Thr1262Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 1,612,162 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 74 hom. )

Consequence

STIL
NM_001048166.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.132

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 1-47251217-C-T is Benign according to our data. Variant chr1-47251217-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 94097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.132 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00512 (779/152294) while in subpopulation SAS AF = 0.019 (92/4830). AF 95% confidence interval is 0.0159. There are 3 homozygotes in GnomAd4. There are 405 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIL	NM_001048166.1 link	c.3786G>A	p.Thr1262Thr	synonymous_variant	Exon 17 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.3786G>A	p.Thr1262Thr	synonymous_variant	Exon 17 of 17	1	NM_001048166.1	ENSP00000360944.3		Q15468-2

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00710

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00742

AC:

1855

AN:

250004

AF XY:

0.00867

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00502

Gnomad ASJ exome

AF:

0.00880

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00375

Gnomad NFE exome

AF:

0.00684

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.00727

AC:

10620

AN:

1459868

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

5686

AN XY:

726054

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33292

American (AMR)

AF:

0.00534

AC:

237

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.00794

AC:

207

AN:

26072

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39680

South Asian (SAS)

AF:

0.0224

AC:

1926

AN:

85792

European-Finnish (FIN)

AF:

0.00348

AC:

186

AN:

53398

Middle Eastern (MID)

AF:

0.0162

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00675

AC:

7498

AN:

1111208

Other (OTH)

AF:

0.00720

AC:

434

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

578

1156

1734

2312

2890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.00512

AC:

779

AN:

152294

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41556

American (AMR)

AF:

0.00484

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0190

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00709

AC:

482

AN:

68024

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00632

Hom.:

Bravo

AF:

0.00516

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00664

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 16, 2017

Athena Diagnostics

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

- -

not specified

Benign:2

Jan 04, 2016

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

- -

Microcephaly 7, primary, autosomal recessive

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.4

(source)

DANN

Benign

0.54

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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