rs141600901

Positions:

• chr15-48739002-AAC-A
• chr15-48739002-AAC-AACAC

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_Strong BP6_Very_Strong BS1 BS2

The NM_001194998.2(CEP152):​c.4378_4379del​(p.Val1460PhefsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,614,180 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (7 hom.)
• Consequence: CEP152 NM_001194998.2 frameshift
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:5
• 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 -12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.147 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BP6: Variant 15-48739002-AAC-A is Benign according to our data. Variant chr15-48739002-AAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 31033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-48739002-AAC-A is described in Lovd as [Pathogenic].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00412 (628/152330) while in subpopulation AFR AF= 0.0146 (608/41576). AF 95% confidence interval is 0.0137. There are 3 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.4378_4379del	p.Val1460PhefsTer3	frameshift_variant	27/27	ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.4378_4379del	p.Val1460PhefsTer3	frameshift_variant	27/27	1	NM_001194998.2	A2
CEP152	ENST00000399334.7	c.4210_4211del	p.Val1404PhefsTer3	frameshift_variant	26/26	1		P2
CEP152	ENST00000561245.1	c.142+2627_142+2628del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152212 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00108 AC: 270 AN: 249228 Hom.: 4 AF XY: 0.000814 AC XY: 110 AN XY: 135196

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000391 AC: 572 AN: 1461850 Hom.: 7 AF XY: 0.000351 AC XY: 255 AN XY: 727218

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.00412 AC: 628 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00381 AC XY: 284 AN XY: 74476

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000554 Hom.: 0

Bravo AF: 0.00459

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	CEP152: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2020	This variant is associated with the following publications: (PMID: 21131973) -

Seckel syndrome 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2011

- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

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: rs141600901; hg19: chr15-49031199;