rs1229

Positions:

• chr2-65084304-G-A

Variant summary

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

The ENST00000377990.7(CEP68):​c.*670G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,112 control chromosomes in the GnomAD database, including 2,231 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 (2231 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP68 ENST00000377990.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.*670G>A		3_prime_UTR_variant	7/7	ENST00000377990.7	NP_055962.2
CEP68	NM_001319100.2	c.*670G>A		3_prime_UTR_variant	7/7		NP_001306029.1
CEP68	NM_001319101.2	c.*670G>A		3_prime_UTR_variant	7/7		NP_001306030.1
CEP68	NR_134966.2	n.3006G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.*670G>A		3_prime_UTR_variant	7/7	1	NM_015147.3	ENSP00000367229	P2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24843 AN: 151994 Hom.: 2226 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.172

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24886 AN: 152112 Hom.: 2231 Cov.: 32 AF XY: 0.163 AC XY: 12154 AN XY: 74384

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.176

Alfa AF: 0.155 Hom.: 386

Bravo AF: 0.164

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.021
DANN	Benign	0.57

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: rs1229; hg19: chr2-65311438;