15-48791380-C-T

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.833-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,607,084 control chromosomes in the GnomAD database, including 157,597 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 0.40 ( 12474 hom., cov: 31)

Exomes 𝑓: 0.44 ( 145123 hom. )

Consequence

CEP152
NM_001194998.2 splice_region, intron

Scores

Splicing: ADA: 0.00002314

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.136

Publications

11 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=-0.82).

BP6

Variant 15-48791380-C-T is Benign according to our data. Variant chr15-48791380-C-T is described in ClinVar as Benign. ClinVar VariationId is 158274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.833-4G>A		splice_region_variant, intron_variant	Intron 7 of 26	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CEP152	ENST00000380950.7 link	c.833-4G>A	splice_region_variant, intron_variant	Intron 7 of 26	1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7 link	c.833-4G>A	splice_region_variant, intron_variant	Intron 7 of 25	1		ENSP00000382271.3
CEP152	ENST00000325747.9 link	c.554-4G>A	splice_region_variant, intron_variant	Intron 6 of 24	1		ENSP00000321000.5
CEP152	ENST00000560322.5 link	n.833-4G>A	splice_region_variant, intron_variant	Intron 7 of 12	1		ENSP00000453440.1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60237

AN:

151566

Hom.:

12474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.444

GnomAD2 exomes

AF:

0.399

AC:

98822

AN:

247492

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.451

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.442

AC:

643661

AN:

1455398

Hom.:

145123

Cov.:

AF XY:

0.442

AC XY:

319984

AN XY:

724310

show subpopulations

African (AFR)

AF:

0.300

AC:

10037

AN:

33402

American (AMR)

AF:

0.330

AC:

14753

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

12809

AN:

26086

East Asian (EAS)

AF:

0.333

AC:

13178

AN:

39590

South Asian (SAS)

AF:

0.397

AC:

34158

AN:

86088

European-Finnish (FIN)

AF:

0.327

AC:

16681

AN:

51066

Middle Eastern (MID)

AF:

0.478

AC:

2747

AN:

5750

European-Non Finnish (NFE)

AF:

0.463

AC:

512849

AN:

1108524

Other (OTH)

AF:

0.439

AC:

26449

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

16039

32078

48117

64156

80195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15206

30412

45618

60824

76030

<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:

0.397

AC:

60248

AN:

151686

Hom.:

12474

Cov.:

AF XY:

0.390

AC XY:

28909

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.310

AC:

12796

AN:

41322

American (AMR)

AF:

0.406

AC:

6198

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1751

AN:

3470

East Asian (EAS)

AF:

0.335

AC:

1727

AN:

5158

South Asian (SAS)

AF:

0.370

AC:

1767

AN:

4780

European-Finnish (FIN)

AF:

0.322

AC:

3382

AN:

10488

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.457

AC:

31062

AN:

67900

Other (OTH)

AF:

0.439

AC:

928

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1785

3571

5356

7142

8927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.449

Hom.:

6272

Bravo

AF:

0.402

Asia WGS

AF:

0.289

AC:

1007

AN:

3476

EpiCase

AF:

0.472

EpiControl

AF:

0.487

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Microcephaly 9, primary, autosomal recessive

Benign:1

Jan 12, 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 12, 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

-0.82

CADD

Benign

9.4

(source)

DANN

Benign

0.44

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.012

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