chr15-48805535-CTTTTT-C

Position:

• chr15-48805535-CTTTTT-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001194998.2(CEP152):​c.87+23_87+27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,239,628 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000235 (265/1128110) while in subpopulation MID AF= 0.0027 (11/4076). AF 95% confidence interval is 0.00151. There are 1 homozygotes in gnomad4_exome. There are 125 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.87+23_87+27del		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+23_87+27del		intron_variant		1	NM_001194998.2	ENSP00000370337	A2

Frequencies

GnomAD3 genomes AF: 0.000233 AC: 26 AN: 111502 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000606

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000887

Gnomad ASJ AF: 0.000452

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000434

Gnomad OTH AF: 0.000683

GnomAD3 exomes AF: 0.000469 AC: 46 AN: 98152 Hom.: 0 AF XY: 0.000391 AC XY: 21 AN XY: 53738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.000809

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000155

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000461

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000235 AC: 265 AN: 1128110 Hom.: 1 AF XY: 0.000221 AC XY: 125 AN XY: 564842

Gnomad4 AFR exome AF: 0.000193

Gnomad4 AMR exome AF: 0.000836

Gnomad4 ASJ exome AF: 0.000556

Gnomad4 EAS exome AF: 0.0000326

Gnomad4 SAS exome AF: 0.0000870

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.000519

GnomAD4 genome AF: 0.000233 AC: 26 AN: 111518 Hom.: 0 Cov.: 0 AF XY: 0.000129 AC XY: 7 AN XY: 54136

Gnomad4 AFR AF: 0.0000605

Gnomad4 AMR AF: 0.0000886

Gnomad4 ASJ AF: 0.000452

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000434

Gnomad4 OTH AF: 0.000678

ClinVar

Not reported in ClinVar

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;