rs12914304

Positions:

• chr15-48721346-T-A

Variant summary

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

The ENST00000561245.1(CEP152):​c.143-4177A>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,836 control chromosomes in the GnomAD database, including 14,297 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 0.41 (14297 hom., cov: 30)
• Consequence: CEP152 ENST00000561245.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724

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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000561245.1	c.143-4177A>T		intron_variant, NMD_transcript_variant		2		ENSP00000453591

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62088 AN: 151718 Hom.: 14291 Cov.: 30

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.409 AC: 62101 AN: 151836 Hom.: 14297 Cov.: 30 AF XY: 0.409 AC XY: 30331 AN XY: 74162

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.421

Alfa AF: 0.463 Hom.: 2150

Bravo AF: 0.384

Asia WGS AF: 0.302 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12914304; hg19: chr15-49013543;