chr15-48783721-T-C

Position:

• chr15-48783721-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001194998.2(CEP152):​c.1321+252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 149,444 control chromosomes in the GnomAD database, including 2,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2563 hom., cov: 30)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-48783721-T-C is Benign according to our data. Variant chr15-48783721-T-C is described in ClinVar as [Benign]. Clinvar id is 668868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.1321+252A>G		intron_variant		ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.1321+252A>G		intron_variant		1	NM_001194998.2	A2
	ENST00000558304.1	n.183-177T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24626 AN: 149402 Hom.: 2563 Cov.: 30

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.165 AC: 24620 AN: 149444 Hom.: 2563 Cov.: 30 AF XY: 0.159 AC XY: 11610 AN XY: 72894

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.00156

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.203

Alfa AF: 0.216 Hom.: 1800

Bravo AF: 0.161

Asia WGS AF: 0.0690 AC: 238 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.65

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: rs11631496; hg19: chr15-49075918;