rs2289181

Positions:

chr15-48797978-G-A

Variant summary

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

The NM_001194998.2(CEP152):c.161C>T(p.Ser54Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0233 in 1,613,918 control chromosomes in the GnomAD database, including 2,498 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. S54S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.029 ( 269 hom., cov: 32)

Exomes 𝑓: 0.023 ( 2229 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

CEP152 (HGNC:29298): (centrosomal protein 152) This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

CEP152 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=0.0014413595).

BP6

Variant 15-48797978-G-A is Benign according to our data. Variant chr15-48797978-G-A is described in ClinVar as [Benign]. Clinvar id is 136719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48797978-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2 linkuse as main transcript	c.161C>T	p.Ser54Leu	missense_variant	3/27	ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7 linkuse as main transcript	c.161C>T	p.Ser54Leu	missense_variant	3/27	1	NM_001194998.2	A2	O94986-4

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4368

AN:

152138

Hom.:

265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.00670

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0591

AC:

14720

AN:

249202

Hom.:

1265

AF XY:

0.0561

AC XY:

7588

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.00989

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.0246

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.00705

Gnomad NFE exome

AF:

0.00543

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0228

AC:

33286

AN:

1461662

Hom.:

2229

Cov.:

AF XY:

0.0249

AC XY:

18077

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00854

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.00698

Gnomad4 NFE exome

AF:

0.00474

Gnomad4 OTH exome

AF:

0.0297

GnomAD4 genome

AF:

0.0287

AC:

4375

AN:

152256

Hom.:

269

Cov.:

AF XY:

0.0336

AC XY:

2499

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.00670

Gnomad4 NFE

AF:

0.00512

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0167

Hom.:

302

Bravo

AF:

0.0346

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.0101

AC:

ESP6500EA

AF:

0.00610

AC:

ExAC

AF:

0.0531

AC:

6419

Asia WGS

AF:

0.168

AC:

582

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00516

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Microcephaly 9, primary, autosomal recessive

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Seckel syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

T;.;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

T;T;T;D

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.1

M;M;M;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.023

D;D;T;D

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

1.0

D;.;B;.

Vest4

0.075

MPC

0.072

ClinPred

0.034

GERP RS

3.7

Varity_R

0.11

gMVP

0.30

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