rs12914304

Variant names:

• chr15-48721346-T-A
• rs12914304
• ENST00000561245.1:n.143-4177A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561245.1(CEP152):​n.143-4177A>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724
• Publications: 0 publications found

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]

CEP152 Gene-Disease associations (from GenCC):

• microcephaly with or without short stature

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Seckel syndrome 5

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• microcephaly 9, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Seckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561245.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP152	ENST00000561245.1	TSL:2	n.143-4177A>T		intron	N/A	ENSP00000453591.1	H0YMG1

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

African (AFR) AF: 0.226 AC: 9357 AN: 41418

American (AMR) AF: 0.373 AC: 5688 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1900 AN: 3462

East Asian (EAS) AF: 0.118 AC: 609 AN: 5170

South Asian (SAS) AF: 0.469 AC: 2242 AN: 4784

European-Finnish (FIN) AF: 0.553 AC: 5805 AN: 10506

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34964 AN: 67930

Other (OTH) AF: 0.421 AC: 886 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		0.72

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12914304;

hg19: chr15-49013543;