Variant rs75503597 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000380950.7(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
ENST00000380950.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

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:

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 (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 id is 158236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48797937-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2 linkuse as main transcript	c.191+11G>A		intron_variant		ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7 linkuse as main transcript	c.191+11G>A		intron_variant		1	NM_001194998.2	ENSP00000370337	A2	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

GnomAD3 exomes

AF:

0.0350

AC:

8697

AN:

248324

Hom.:

264

AF XY:

0.0355

AC XY:

4782

AN XY:

134692

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 SAS exome

AF:

0.0328

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

Gnomad4 AFR exome

AF:

0.00294

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.0791

Gnomad4 SAS exome

AF:

0.0344

Gnomad4 FIN exome

AF:

0.0970

Gnomad4 NFE exome

AF:

0.0247

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0252

AC:

3838

AN:

152230

Hom.:

112

Cov.:

AF XY:

0.0291

AC XY:

2165

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00462

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.0805

Gnomad4 SAS

AF:

0.0335

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.0251

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0229

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

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+	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

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

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.54

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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