chr15-48752341-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001194998.2(CEP152):c.3466+8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,764 control chromosomes in the GnomAD database, including 28,309 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 7186 hom., cov: 32)

Exomes 𝑓: 0.15 ( 21123 hom. )

Consequence

CEP152
NM_001194998.2 splice_region, intron

Scores

Splicing: ADA: 0.000004609

Clinical Significance

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

Conservation

PhyloP100: 0.533

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

microcephaly with or without short stature
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Seckel syndrome 5
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
microcephaly 9, primary, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP152 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 15-48752341-C-G is Benign according to our data. Variant chr15-48752341-C-G is described in ClinVar as Benign. ClinVar VariationId is 95653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.3466+8G>C		splice_region_variant, intron_variant	Intron 21 of 26	ENST00000380950.7	NP_001181927.1	O94986-4Q3B7A2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP152	ENST00000380950.7 link	c.3466+8G>C	splice_region_variant, intron_variant	Intron 21 of 26	1	NM_001194998.2	ENSP00000370337.2	O94986-4
CEP152	ENST00000399334.7 link	c.3466+8G>C	splice_region_variant, intron_variant	Intron 21 of 25	1		ENSP00000382271.3	O94986-3
CEP152	ENST00000325747.9 link	c.3187+8G>C	splice_region_variant, intron_variant	Intron 20 of 24	1		ENSP00000321000.5	O94986-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38280

AN:

151916

Hom.:

7161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.0819

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.207

GnomAD2 exomes

AF:

0.194

AC:

48442

AN:

249462

AF XY:

0.182

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.0827

Gnomad EAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.147

AC:

214448

AN:

1461728

Hom.:

21123

Cov.:

AF XY:

0.144

AC XY:

104944

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.530

AC:

17745

AN:

33472

American (AMR)

AF:

0.234

AC:

10470

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0797

AC:

2082

AN:

26136

East Asian (EAS)

AF:

0.446

AC:

17715

AN:

39692

South Asian (SAS)

AF:

0.135

AC:

11609

AN:

86252

European-Finnish (FIN)

AF:

0.138

AC:

7361

AN:

53402

Middle Eastern (MID)

AF:

0.127

AC:

720

AN:

5688

European-Non Finnish (NFE)

AF:

0.123

AC:

136830

AN:

1111986

Other (OTH)

AF:

0.164

AC:

9916

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

10733

21466

32198

42931

53664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5318

10636

15954

21272

26590

<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:

0.252

AC:

38338

AN:

152036

Hom.:

7186

Cov.:

AF XY:

0.251

AC XY:

18665

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.514

AC:

21307

AN:

41458

American (AMR)

AF:

0.189

AC:

2892

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0819

AC:

284

AN:

3466

East Asian (EAS)

AF:

0.472

AC:

2433

AN:

5160

South Asian (SAS)

AF:

0.154

AC:

740

AN:

4818

European-Finnish (FIN)

AF:

0.142

AC:

1503

AN:

10558

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8541

AN:

67964

Other (OTH)

AF:

0.205

AC:

432

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1247

2494

3740

4987

6234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.113

Hom.:

434

Bravo

AF:

0.274

Asia WGS

AF:

0.296

AC:

1028

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Dec 18, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Microcephaly 9, primary, autosomal recessive

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Seckel syndrome 5

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.7

(source)

DANN

Benign

0.42

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000046

dbscSNV1_RF

Benign

0.0

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