rs4482220

Positions:

• chr15-48809634-G-A

Variant summary

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

The NM_001194998.2(CEP152):​c.-8+1327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,118 control chromosomes in the GnomAD database, including 4,013 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 0.21 (4013 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.-8+1327C>T		intron_variant		ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.-8+1327C>T		intron_variant		1	NM_001194998.2	A2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32072 AN: 152000 Hom.: 4012 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32093 AN: 152118 Hom.: 4013 Cov.: 32 AF XY: 0.214 AC XY: 15893 AN XY: 74376

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0822

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.190

Alfa AF: 0.247 Hom.: 4557

Bravo AF: 0.189

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.51

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: rs4482220; hg19: chr15-49101831;