15-48740502-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001194998.2(CEP152):c.4093+1099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 151,980 control chromosomes in the GnomAD database, including 53,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (53589 hom., cov: 30)
  • Exomes 𝑓: 0.68 (8 hom.)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.4093+1099G>A		intron_variant		ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.4093+1099G>A		intron_variant		1	NM_001194998.2	A2
CEP152	ENST00000399334.7	c.3925+1099G>A		intron_variant		1		P2
CEP152	ENST00000561245.1	c.142+1129G>A		intron_variant, NMD_transcript_variant		2
CEP152	ENST00000325747.9			downstream_gene_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126852 AN: 151834 Hom.: 53531 Cov.: 30

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.794

GnomAD4 exome AF: 0.679 AC: 19 AN: 28 Hom.: 8 Cov.: 0 AF XY: 0.857 AC XY: 12 AN XY: 14

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.836 AC: 126969 AN: 151952 Hom.: 53589 Cov.: 30 AF XY: 0.841 AC XY: 62501 AN XY: 74282

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.797

Alfa AF: 0.771 Hom.: 41134

Bravo AF: 0.838

Asia WGS AF: 0.933 AC: 3239 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.8
Dann	Benign	0.50

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: rs784405; hg19: chr15-49032699;