15-48767886-G-T

Position:

• chr15-48767886-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001194998.2(CEP152):​c.2018+333C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 152,156 control chromosomes in the GnomAD database, including 357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.037 (357 hom., cov: 32)
• Consequence: CEP152 NM_001194998.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.616

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=-0.3).
• BP6: Variant 15-48767886-G-T is Benign according to our data. Variant chr15-48767886-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 669844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP152	NM_001194998.2	c.2018+333C>A		intron_variant		ENST00000380950.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP152	ENST00000380950.7	c.2018+333C>A		intron_variant		1	NM_001194998.2	A2
CEP152	ENST00000325747.9	c.1739+333C>A		intron_variant		1		A2
CEP152	ENST00000399334.7	c.2018+333C>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5644 AN: 152038 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.000756

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00453

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0372 AC: 5663 AN: 152156 Hom.: 357 Cov.: 32 AF XY: 0.0416 AC XY: 3098 AN XY: 74386

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.000756

Gnomad4 NFE AF: 0.00453

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.00180 Hom.: 0

Bravo AF: 0.0476

Asia WGS AF: 0.167 AC: 579 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

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	-0.30
CADD	Benign	16
DANN	Benign	0.76

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: rs16961610; hg19: chr15-49060083;