rs78945874

Positions:

• chr2-65082305-A-G

Variant summary

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

The ENST00000377990.7(CEP68):​c.2105-231A>G 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 152,258 control chromosomes in the GnomAD database, including 1,109 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 (1109 hom., cov: 33)
• Consequence: CEP68 ENST00000377990.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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=-0.83).
• 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.2105-231A>G		intron_variant		ENST00000377990.7	NP_055962.2
CEP68	NM_001319100.2	c.2105-231A>G		intron_variant			NP_001306029.1
CEP68	NM_001319101.2	c.1694-231A>G		intron_variant			NP_001306030.1
CEP68	NR_134966.2	n.2167-231A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.2105-231A>G		intron_variant		1	NM_015147.3	ENSP00000367229	P2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15719 AN: 152140 Hom.: 1110 Cov.: 33

Gnomad AFR AF: 0.0240

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: 0.144

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.103 AC: 15723 AN: 152258 Hom.: 1109 Cov.: 33 AF XY: 0.104 AC XY: 7779 AN XY: 74442

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.128

Alfa AF: 0.126 Hom.: 172

Bravo AF: 0.0956

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.40

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: rs78945874; hg19: chr2-65309439;