rs76221156

chr2-65077395-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.2008-473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,160 control chromosomes in the GnomAD database, including 1,091 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 (1091 hom., cov: 31)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP68	NM_015147.3	c.2008-473C>T		intron_variant		ENST00000377990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP68	ENST00000377990.7	c.2008-473C>T		intron_variant		1	NM_015147.3	P2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15605 AN: 152042 Hom.: 1092 Cov.: 31

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15609 AN: 152160 Hom.: 1091 Cov.: 31 AF XY: 0.104 AC XY: 7741 AN XY: 74372

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.125

Alfa AF: 0.126 Hom.: 172

Bravo AF: 0.0947

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	13
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: rs76221156; hg19: chr2-65304529;