chr15-48756508-G-C

Position:

chr15-48756508-G-C

Variant summary

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

The NM_001194998.2(CEP152):c.2740C>G(p.Leu914Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 1,609,732 control chromosomes in the GnomAD database, including 5,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 370 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4733 hom. )

Consequence

CEP152
NM_001194998.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.829

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:

CEP152 (HGNC:):

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=0.0014411211).

BP6

Variant 15-48756508-G-C is Benign according to our data. Variant chr15-48756508-G-C is described in ClinVar as [Benign]. Clinvar id is 136723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48756508-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2 linkuse as main transcript	c.2740C>G	p.Leu914Val	missense_variant	20/27	ENST00000380950.7	NP_001181927.1	O94986-4Q3B7A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CEP152	ENST00000380950.7 linkuse as main transcript	c.2740C>G	p.Leu914Val	missense_variant	20/27	1	NM_001194998.2	ENSP00000370337.2	O94986-4
CEP152	ENST00000399334.7 linkuse as main transcript	c.2740C>G	p.Leu914Val	missense_variant	20/26	1		ENSP00000382271.3	O94986-3
CEP152	ENST00000325747.9 linkuse as main transcript	c.2461C>G	p.Leu821Val	missense_variant	19/25	1		ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes

AF:

0.0613

AC:

9308

AN:

151928

Hom.:

370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.0715

Gnomad SAS

AF:

0.0698

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0776

Gnomad OTH

AF:

0.0579

GnomAD3 exomes

AF:

0.0717

AC:

17658

AN:

246118

Hom.:

763

AF XY:

0.0744

AC XY:

9949

AN XY:

133800

show subpopulations

Gnomad AFR exome

AF:

0.0139

Gnomad AMR exome

AF:

0.0302

Gnomad ASJ exome

AF:

0.0630

Gnomad EAS exome

AF:

0.0754

Gnomad SAS exome

AF:

0.0673

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0699

GnomAD4 exome

AF:

0.0775

AC:

112989

AN:

1457686

Hom.:

4733

Cov.:

AF XY:

0.0777

AC XY:

56326

AN XY:

725316

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.0318

Gnomad4 ASJ exome

AF:

0.0597

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.0703

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.0804

Gnomad4 OTH exome

AF:

0.0693

GnomAD4 genome

AF:

0.0612

AC:

9305

AN:

152046

Hom.:

370

Cov.:

AF XY:

0.0648

AC XY:

4818

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.0715

Gnomad4 SAS

AF:

0.0698

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.0776

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0594

Hom.:

115

Bravo

AF:

0.0513

TwinsUK

AF:

0.0747

AC:

277

ALSPAC

AF:

0.0781

AC:

301

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0741

AC:

603

ExAC

AF:

0.0724

AC:

8748

Asia WGS

AF:

0.0600

AC:

210

AN:

3478

EpiCase

AF:

0.0715

EpiControl

AF:

0.0706

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2013	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	- -
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+	-	- -

not provided

Benign:2

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	- -

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. -

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

0.086

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0074

T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0050

B;.;B

Vest4

0.040

MPC

0.073

ClinPred

0.0017

GERP RS

0.32

Varity_R

0.053

gMVP

0.052

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