rs116089174

Positions:

• chr15-48768336-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001194998.2(CEP152):​c.1909-8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,441,726 control chromosomes in the GnomAD database, including 15 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (7 hom.)
• Consequence: CEP152 NM_001194998.2 splice_region, intron
• Scores: Splicing: ADA: 0.00003090
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.433

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 (BayesDel_noAF=-0.82).
• BP6: Variant 15-48768336-C-G is Benign according to our data. Variant chr15-48768336-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 158235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00497 (757/152254) while in subpopulation AFR AF= 0.0175 (729/41542). AF 95% confidence interval is 0.0165. There are 8 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.1909-8G>C		splice_region_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.1909-8G>C		splice_region_variant, intron_variant		1	NM_001194998.2	ENSP00000370337.2
CEP152	ENST00000399334.7	c.1909-8G>C		splice_region_variant, intron_variant		1		ENSP00000382271.3
CEP152	ENST00000325747.9	c.1630-8G>C		splice_region_variant, intron_variant		1		ENSP00000321000.5

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 755 AN: 152136 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00121 AC: 297 AN: 245398 Hom.: 0 AF XY: 0.000946 AC XY: 126 AN XY: 133182

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.000908

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000904

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.000545 AC: 703 AN: 1289472 Hom.: 7 Cov.: 19 AF XY: 0.000481 AC XY: 313 AN XY: 650742

Gnomad4 AFR exome AF: 0.0187

Gnomad4 AMR exome AF: 0.00108

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000485

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000230

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.00497 AC: 757 AN: 152254 Hom.: 8 Cov.: 32 AF XY: 0.00481 AC XY: 358 AN XY: 74452

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00152 Hom.: 0

Bravo AF: 0.00564

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 17, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 2015	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. -

CEP152-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: rs116089174; hg19: chr15-49060533;