chr15-48791380-C-T

Position:

• chr15-48791380-C-T

Variant summary

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

The ENST00000380950.7(CEP152):​c.833-4G>A variant causes a splice region, splice polypyrimidine tract, 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 ENST00000380950.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002314
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.136

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 158274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48791380-C-T is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.833-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.833-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001194998.2	ENSP00000370337	A2
CEP152	ENST00000325747.9	c.554-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000321000	A2
CEP152	ENST00000399334.7	c.833-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000382271	P2
CEP152	ENST00000560322.5	c.833-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000453440

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60237 AN: 151566 Hom.: 12474 Cov.: 31

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

GnomAD3 exomes AF: 0.399 AC: 98822 AN: 247492 Hom.: 20502 AF XY: 0.408 AC XY: 54789 AN XY: 134424

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 SAS exome AF: 0.388

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.: 33 AF XY: 0.442 AC XY: 319984 AN XY: 724310

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.397 AC: 60248 AN: 151686 Hom.: 12474 Cov.: 31 AF XY: 0.390 AC XY: 28909 AN XY: 74100

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.439

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

Submissions by phenotype

not specified Benign:5

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	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:3

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	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Microcephaly 9, primary, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 12, 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
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs58156069; hg19: chr15-49083577; COSMIC: COSV57857885; COSMIC: COSV57857885;