1-47302242-G-A

Position:

chr1-47302242-G-A

Variant summary

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

The NM_001048166.1(STIL):c.257C>T(p.Ala86Val) variant causes a missense change. The variant allele was found at a frequency of 0.501 in 1,606,720 control chromosomes in the GnomAD database, including 208,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27290 hom., cov: 32)

Exomes 𝑓: 0.49 ( 181655 hom. )

Consequence

STIL
NM_001048166.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: 5.35

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:

STIL (HGNC:):

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=5.9604446E-7).

BP6

Variant 1-47302242-G-A is Benign according to our data. Variant chr1-47302242-G-A is described in ClinVar as [Benign]. Clinvar id is 21354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-47302242-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIL	NM_001048166.1 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	4/17	ENST00000371877.8	NP_001041631.1	Q15468-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIL	ENST00000371877.8 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	4/17	1	NM_001048166.1	ENSP00000360944.3		Q15468-2

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87330

AN:

151862

Hom.:

27255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.498

AC:

125160

AN:

251140

Hom.:

32702

AF XY:

0.488

AC XY:

66245

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.841

Gnomad AMR exome

AF:

0.555

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.494

AC:

718056

AN:

1454740

Hom.:

181655

Cov.:

AF XY:

0.490

AC XY:

355055

AN XY:

724056

show subpopulations

Gnomad4 AFR exome

AF:

0.849

Gnomad4 AMR exome

AF:

0.557

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.581

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.489

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.575

AC:

87411

AN:

151980

Hom.:

27290

Cov.:

AF XY:

0.569

AC XY:

42257

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.831

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.553

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.355

Gnomad4 NFE

AF:

0.479

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.494

Hom.:

47479

Bravo

AF:

0.605

TwinsUK

AF:

0.488

AC:

1809

ALSPAC

AF:

0.492

AC:

1895

ESP6500AA

AF:

0.820

AC:

3612

ESP6500EA

AF:

0.477

AC:

4102

ExAC

AF:

0.502

AC:

60992

Asia WGS

AF:

0.508

AC:

1770

AN:

3478

EpiCase

AF:

0.471

EpiControl

AF:

0.474

ClinVar

Significance: Benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephaly 7, primary, autosomal recessive

Benign:4Other:1

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.25

DEOGEN2

Benign

0.099

T;.;.;.;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.078

T;T;T;T;T;T

MetaRNN

Benign

6.0e-7

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.9

N;.;N;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

3.1

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;.;.

Polyphen

0.0

B;.;B;B;B;.

Vest4

0.14

MPC

0.10

ClinPred

0.011

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.23

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