chr15-48805535-C-CTTT

Position:

• chr15-48805535-C-CTTT

Variant summary

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

The NM_001194998.2(CEP152):​c.87+27_87+28insAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000345 in 1,238,472 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 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 amr. gnomad4_exome allele frequency = 0.000373 (420/1126970) while in subpopulation AMR AF= 0.0032 (103/32156). AF 95% confidence interval is 0.0027. There are 0 homozygotes in gnomad4_exome. There are 213 alleles in male gnomad4_exome subpopulation. Median coverage is 24. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000628 AC: 7 AN: 111502 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000606

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000355

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00194 AC: 190 AN: 98152 Hom.: 1 AF XY: 0.00197 AC XY: 106 AN XY: 53738

Gnomad AFR exome AF: 0.00224

Gnomad AMR exome AF: 0.00555

Gnomad ASJ exome AF: 0.000607

Gnomad EAS exome AF: 0.00369

Gnomad SAS exome AF: 0.00178

Gnomad FIN exome AF: 0.000860

Gnomad NFE exome AF: 0.000737

Gnomad OTH exome AF: 0.00162

GnomAD4 exome AF: 0.000373 AC: 420 AN: 1126970 Hom.: 0 Cov.: 24 AF XY: 0.000378 AC XY: 213 AN XY: 564204

Gnomad4 AFR exome AF: 0.00112

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.000202

Gnomad4 EAS exome AF: 0.00249

Gnomad4 SAS exome AF: 0.000654

Gnomad4 FIN exome AF: 0.000512

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.000368

GnomAD4 genome AF: 0.0000628 AC: 7 AN: 111502 Hom.: 0 Cov.: 26 AF XY: 0.0000185 AC XY: 1 AN XY: 54092

Gnomad4 AFR AF: 0.0000606

Gnomad4 AMR AF: 0.000355

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000238

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;