rs12621608

Positions:

• chr2-65073618-C-T

Variant summary

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

The NM_015147.3(CEP68):​c.1884+638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 161,052 control chromosomes in the GnomAD database, including 2,767 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 0.17 (2612 hom., cov: 32)
  • Exomes 𝑓: 0.18 (155 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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: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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP68	NM_015147.3	c.1884+638C>T		intron_variant		ENST00000377990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP68	ENST00000377990.7	c.1884+638C>T		intron_variant		1	NM_015147.3	P2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25473 AN: 152136 Hom.: 2602 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.175 AC: 1541 AN: 8798 Hom.: 155 Cov.: 0 AF XY: 0.170 AC XY: 767 AN XY: 4512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.0923

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.167 AC: 25499 AN: 152254 Hom.: 2612 Cov.: 32 AF XY: 0.170 AC XY: 12672 AN XY: 74408

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.211

Alfa AF: 0.181 Hom.: 437

Bravo AF: 0.166

Asia WGS AF: 0.366 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.79

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: rs12621608; hg19: chr2-65300752;