chr15-48797978-G-A

Position:

• chr15-48797978-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001194998.2(CEP152):​c.161C>T​(p.Ser54Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0233 in 1,613,918 control chromosomes in the GnomAD database, including 2,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (269 hom., cov: 32)
  • Exomes 𝑓: 0.023 (2229 hom.)
• Consequence: CEP152 NM_001194998.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 3.69

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014413595).
• BP6: Variant 15-48797978-G-A is Benign according to our data. Variant chr15-48797978-G-A is described in ClinVar as [Benign]. Clinvar id is 136719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48797978-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.161C>T	p.Ser54Leu	missense_variant	3/27	ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.161C>T	p.Ser54Leu	missense_variant	3/27	1	NM_001194998.2	ENSP00000370337.2

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4368 AN: 152138 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.00670

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.0340

GnomAD3 exomes AF: 0.0591 AC: 14720 AN: 249202 Hom.: 1265 AF XY: 0.0561 AC XY: 7588 AN XY: 135198

Gnomad AFR exome AF: 0.00989

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.0246

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.00705

Gnomad NFE exome AF: 0.00543

Gnomad OTH exome AF: 0.0355

GnomAD4 exome AF: 0.0228 AC: 33286 AN: 1461662 Hom.: 2229 Cov.: 31 AF XY: 0.0249 AC XY: 18077 AN XY: 727132

Gnomad4 AFR exome AF: 0.00854

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.00698

Gnomad4 NFE exome AF: 0.00474

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0287 AC: 4375 AN: 152256 Hom.: 269 Cov.: 32 AF XY: 0.0336 AC XY: 2499 AN XY: 74448

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.00670

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0167 Hom.: 302

Bravo AF: 0.0346

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.0101 AC: 41

ESP6500EA AF: 0.00610 AC: 51

ExAC AF: 0.0531 AC: 6419

Asia WGS AF: 0.168 AC: 582 AN: 3478

EpiCase AF: 0.00660

EpiControl AF: 0.00516

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

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	- -

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

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T;T;T;D
MetaRNN	Benign	0.0014	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.023	D;D;T;D
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		1.0	D;.;B;.
Vest4		0.075
MPC		0.072
ClinPred		0.034	T
GERP RS		3.7
Varity_R		0.11
gMVP		0.30

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

Other links and lift over

dbSNP: rs2289181; hg19: chr15-49090175; COSMIC: COSV57857900;