chr15-48805535-C-CTT

Position:

• chr15-48805535-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001194998.2(CEP152):​c.87+27_87+28insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00815 in 1,228,752 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 26)
  • Exomes 𝑓: 0.0078 (5 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181

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 -10 ACMG points.

• BP6: Variant 15-48805535-C-CTT is Benign according to our data. Variant chr15-48805535-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1270486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0119 (1322/111476) while in subpopulation AMR AF= 0.0325 (366/11268). AF 95% confidence interval is 0.0297. There are 22 homozygotes in gnomad4. There are 667 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.87+27_87+28insAA		intron_variant		ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.87+27_87+28insAA		intron_variant		1	NM_001194998.2	ENSP00000370337	A2

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1318 AN: 111460 Hom.: 21 Cov.: 26

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.000452

Gnomad EAS AF: 0.0186

Gnomad SAS AF: 0.00470

Gnomad FIN AF: 0.00214

Gnomad MID AF: 0.00435

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.0220 AC: 2159 AN: 98152 Hom.: 5 AF XY: 0.0200 AC XY: 1077 AN XY: 53738

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.0610

Gnomad ASJ exome AF: 0.00505

Gnomad EAS exome AF: 0.0502

Gnomad SAS exome AF: 0.0166

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.00933

Gnomad OTH exome AF: 0.0162

GnomAD4 exome AF: 0.00778 AC: 8693 AN: 1117276 Hom.: 5 Cov.: 24 AF XY: 0.00774 AC XY: 4329 AN XY: 559238

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.0410

Gnomad4 ASJ exome AF: 0.00352

Gnomad4 EAS exome AF: 0.0433

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.00967

Gnomad4 NFE exome AF: 0.00453

Gnomad4 OTH exome AF: 0.00939

GnomAD4 genome AF: 0.0119 AC: 1322 AN: 111476 Hom.: 22 Cov.: 26 AF XY: 0.0123 AC XY: 667 AN XY: 54106

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.000452

Gnomad4 EAS AF: 0.0184

Gnomad4 SAS AF: 0.00472

Gnomad4 FIN AF: 0.00214

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.0102

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs372967874; hg19: chr15-49097732;