rs1894874

Positions:

• chr2-65080245-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.2104+2281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 984,906 control chromosomes in the GnomAD database, including 7,755 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1102 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6653 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB1A (HGNC:):

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.2104+2281T>C		intron_variant		ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.2104+2281T>C		intron_variant		1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15716 AN: 152118 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.124 AC: 103306 AN: 832670 Hom.: 6653 Cov.: 30 AF XY: 0.124 AC XY: 47685 AN XY: 384526

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.103 AC: 15720 AN: 152236 Hom.: 1102 Cov.: 32 AF XY: 0.104 AC XY: 7773 AN XY: 74414

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.128

Alfa AF: 0.126 Hom.: 173

Bravo AF: 0.0957

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.72

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: rs1894874; hg19: chr2-65307379;