rs11927068

chr3-134547479-A-G

Variant summary

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

The NM_001353108.3(CEP63):c.1067+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,610,868 control chromosomes in the GnomAD database, including 81,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7997 hom., cov: 30)
  • Exomes 𝑓: 0.31 (73134 hom.)
• Consequence: CEP63 NM_001353108.3 splice_region, intron
• Scores: Splicing: ADA: 0.00007666
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.33

Genes affected

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 3-134547479-A-G is Benign according to our data. Variant chr3-134547479-A-G is described in ClinVar as [Benign]. Clinvar id is 128706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP63	NM_001353108.3	c.1067+7A>G		splice_region_variant, intron_variant		ENST00000675561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP63	ENST00000675561.1	c.1067+7A>G		splice_region_variant, intron_variant			NM_001353108.3	A1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48398 AN: 151786 Hom.: 7996 Cov.: 30

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.329

GnomAD3 exomes AF: 0.287 AC: 71958 AN: 250730 Hom.: 10938 AF XY: 0.295 AC XY: 39903 AN XY: 135492

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.297

GnomAD4 exome AF: 0.314 AC: 457438 AN: 1458964 Hom.: 73134 Cov.: 33 AF XY: 0.315 AC XY: 228791 AN XY: 726026

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.319 AC: 48425 AN: 151904 Hom.: 7997 Cov.: 30 AF XY: 0.313 AC XY: 23197 AN XY: 74208

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.329

Alfa AF: 0.319 Hom.: 3432

Bravo AF: 0.317

Asia WGS AF: 0.245 AC: 851 AN: 3478

EpiCase AF: 0.329

EpiControl AF: 0.329

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 14, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 23, 2017	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	7.3
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000077
dbscSNV1_RF	Benign	0.0
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: rs11927068; hg19: chr3-134266321; COSMIC: COSV59675037; COSMIC: COSV59675037;