rs75503597

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.191+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,608,296 control chromosomes in the GnomAD database, including 1,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 112 hom., cov: 32)

Exomes 𝑓: 0.028 ( 905 hom. )

Consequence

CEP152
NM_001194998.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

Publications

2 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=-0.88).

BP6

Variant 15-48797937-C-T is Benign according to our data. Variant chr15-48797937-C-T is described in ClinVar as Benign. ClinVar VariationId is 158236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.191+11G>A		intron_variant	Intron 3 of 26	ENST00000380950.7	NP_001181927.1	O94986-4Q3B7A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7 link	c.191+11G>A		intron_variant	Intron 3 of 26	1	NM_001194998.2	ENSP00000370337.2		O94986-4

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3840

AN:

152112

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.0805

Gnomad SAS

AF:

0.0335

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0350

AC:

8697

AN:

248324

AF XY:

0.0355

show subpopulations

Gnomad AFR exome

AF:

0.00421

Gnomad AMR exome

AF:

0.00673

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.0883

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0284

AC:

41372

AN:

1456066

Hom.:

905

Cov.:

AF XY:

0.0287

AC XY:

20820

AN XY:

724674

show subpopulations

African (AFR)

AF:

0.00294

AC:

AN:

33330

American (AMR)

AF:

0.00760

AC:

339

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

379

AN:

26102

East Asian (EAS)

AF:

0.0791

AC:

3138

AN:

39666

South Asian (SAS)

AF:

0.0344

AC:

2958

AN:

86000

European-Finnish (FIN)

AF:

0.0970

AC:

5175

AN:

53352

Middle Eastern (MID)

AF:

0.0210

AC:

121

AN:

5752

European-Non Finnish (NFE)

AF:

0.0247

AC:

27382

AN:

1107092

Other (OTH)

AF:

0.0296

AC:

1782

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2116

4233

6349

8466

10582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1054

2108

3162

4216

5270

<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:

0.0252

AC:

3838

AN:

152230

Hom.:

112

Cov.:

AF XY:

0.0291

AC XY:

2165

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00462

AC:

192

AN:

41548

American (AMR)

AF:

0.00980

AC:

150

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3468

East Asian (EAS)

AF:

0.0805

AC:

417

AN:

5182

South Asian (SAS)

AF:

0.0335

AC:

162

AN:

4830

European-Finnish (FIN)

AF:

0.105

AC:

1112

AN:

10568

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0251

AC:

1704

AN:

68016

Other (OTH)

AF:

0.0199

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

188

376

563

751

939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0215

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.0510

AC:

175

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephaly 9, primary, autosomal recessive

Benign:1

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. -

Seckel syndrome 5

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

-0.88

CADD

Benign

0.54

(source)

DANN

Benign

0.46

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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