15-48717160-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000561245.1(CEP152):c.152C>A(p.Ala51Asp) variant causes a missense, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0073 in 455,410 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0068 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (12 hom.)
• Consequence: CEP152 ENST00000561245.1 missense, NMD_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-48717160-G-T is Benign according to our data. Variant chr15-48717160-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0068 (1032/151704) while in subpopulation NFE AF= 0.00937 (637/67988). AF 95% confidence interval is 0.00877. There are 8 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000561245.1	c.152C>A	p.Ala51Asp	missense_variant, NMD_transcript_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.00679 AC: 1030 AN: 151600 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00189

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00887

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00562

Gnomad FIN AF: 0.00720

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.00937

Gnomad OTH AF: 0.0106

GnomAD3 exomes AF: 0.00631 AC: 807 AN: 127982 Hom.: 4 AF XY: 0.00629 AC XY: 441 AN XY: 70088

Gnomad AFR exome AF: 0.00198

Gnomad AMR exome AF: 0.00707

Gnomad ASJ exome AF: 0.00247

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00550

Gnomad FIN exome AF: 0.00613

Gnomad NFE exome AF: 0.00875

Gnomad OTH exome AF: 0.00827

GnomAD4 exome AF: 0.00754 AC: 2291 AN: 303706 Hom.: 12 Cov.: 0 AF XY: 0.00731 AC XY: 1264 AN XY: 172956

Gnomad4 AFR exome AF: 0.00232

Gnomad4 AMR exome AF: 0.00697

Gnomad4 ASJ exome AF: 0.00278

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00551

Gnomad4 FIN exome AF: 0.00760

Gnomad4 NFE exome AF: 0.00939

Gnomad4 OTH exome AF: 0.00781

GnomAD4 genome AF: 0.00680 AC: 1032 AN: 151704 Hom.: 8 Cov.: 32 AF XY: 0.00671 AC XY: 497 AN XY: 74086

Gnomad4 AFR AF: 0.00189

Gnomad4 AMR AF: 0.00886

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00604

Gnomad4 FIN AF: 0.00720

Gnomad4 NFE AF: 0.00937

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.00564 Hom.: 2

Bravo AF: 0.00646

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

CEP152: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs145377591; hg19: chr15-49009357;