15-48811047-T-C

Variant names:

Variant summary

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

The ENST00000560322.5(CEP152):n.-94A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,338 control chromosomes in the GnomAD database, including 1,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1547 hom., cov: 33)

Exomes 𝑓: 0.073 ( 1 hom. )

Consequence

CEP152
ENST00000560322.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.581

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:

ENSG00000259700 (HGNC:):

ENSG00000259700 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=-0.85).

BP6

Variant 15-48811047-T-C is Benign according to our data. Variant chr15-48811047-T-C is described in ClinVar as Benign. ClinVar VariationId is 316436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP152	NM_001194998.2 link	c.-94A>G		5_prime_UTR_variant	Exon 1 of 27	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.-94A>G		5_prime_UTR_variant	Exon 1 of 27	1	NM_001194998.2	ENSP00000370337.2		O94986-4

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18914

AN:

152138

Hom.:

1535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.0694

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.0885

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.0732

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0370

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0323

AC:

AN:

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.124

AC:

18954

AN:

152256

Hom.:

1547

Cov.:

AF XY:

0.131

AC XY:

9746

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.144

AC:

5984

AN:

41552

American (AMR)

AF:

0.235

AC:

3589

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0694

AC:

241

AN:

3472

East Asian (EAS)

AF:

0.296

AC:

1523

AN:

5152

South Asian (SAS)

AF:

0.208

AC:

1006

AN:

4828

European-Finnish (FIN)

AF:

0.0885

AC:

940

AN:

10624

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0787

AC:

5351

AN:

68012

Other (OTH)

AF:

0.130

AC:

275

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

837

1674

2510

3347

4184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0981

Hom.:

1630

Bravo

AF:

0.138

Asia WGS

AF:

0.278

AC:

965

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 23, 2020

GeneDx

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

- -

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

-0.85

CADD

Benign

4.2

(source)

DANN

Benign

0.70

PhyloP100

-0.58

PromoterAI

-0.096

Neutral

(source)

Mutation Taster

=204/96

polymorphism (auto)

(source)

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over