rs1426200

Positions:

• chr15-48805819-C-A
• chr15-48805819-C-G
• chr15-48805819-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000380950.7(CEP152):​c.-7-163G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,200 control chromosomes in the GnomAD database, including 56,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.86 (56092 hom., cov: 32)
• Consequence: CEP152 ENST00000380950.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.437

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-48805819-C-A is Benign according to our data. Variant chr15-48805819-C-A is described in ClinVar as [Benign]. Clinvar id is 678332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP152	NM_001194998.2	c.-7-163G>T		intron_variant		ENST00000380950.7	NP_001181927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP152	ENST00000380950.7	c.-7-163G>T		intron_variant		1	NM_001194998.2	ENSP00000370337	A2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130196 AN: 152082 Hom.: 56042 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.856 AC: 130301 AN: 152200 Hom.: 56092 Cov.: 32 AF XY: 0.861 AC XY: 64075 AN XY: 74406

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.870

Alfa AF: 0.849 Hom.: 7801

Bravo AF: 0.853

Asia WGS AF: 0.957 AC: 3329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	3.5
DANN	Benign	0.60

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: rs1426200; hg19: chr15-49098016;