rs1050675

Positions:

• chr2-65083897-A-G

Variant summary

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

The NM_015147.3(CEP68):​c.*263A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,164 control chromosomes in the GnomAD database, including 2,058 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 0.16 (2058 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CEP68 NM_015147.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530

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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.*263A>G		3_prime_UTR_variant	7/7	ENST00000377990.7	NP_055962.2
CEP68	NM_001319100.2	c.*263A>G		3_prime_UTR_variant	7/7		NP_001306029.1
CEP68	NM_001319101.2	c.*263A>G		3_prime_UTR_variant	7/7		NP_001306030.1
CEP68	NR_134966.2	n.2599A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.*263A>G		3_prime_UTR_variant	7/7	1	NM_015147.3	ENSP00000367229	P2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24070 AN: 152044 Hom.: 2055 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.158 AC: 24102 AN: 152162 Hom.: 2058 Cov.: 32 AF XY: 0.158 AC XY: 11773 AN XY: 74390

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.172

Alfa AF: 0.148 Hom.: 1023

Bravo AF: 0.158

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.84

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: rs1050675; hg19: chr2-65311031;