rs10496123

chr2-65082162-G-Achr2-65082162-G-C

Variant summary

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

The NM_015147.3(CEP68):c.2105-374G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,160 control chromosomes in the GnomAD database, including 4,089 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 0.21 (4089 hom., cov: 33)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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 (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP68	NM_015147.3	c.2105-374G>A		intron_variant		ENST00000377990.7
CEP68	NM_001319100.2	c.2105-374G>A		intron_variant
CEP68	NM_001319101.2	c.1694-374G>A		intron_variant
CEP68	NR_134966.2	n.2167-374G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP68	ENST00000377990.7	c.2105-374G>A		intron_variant		1	NM_015147.3	P2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32391 AN: 152042 Hom.: 4085 Cov.: 33

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.213 AC: 32396 AN: 152160 Hom.: 4089 Cov.: 33 AF XY: 0.215 AC XY: 15968 AN XY: 74370

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.212

Alfa AF: 0.259 Hom.: 7862

Bravo AF: 0.201

Asia WGS AF: 0.244 AC: 850 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	2.1
Dann	Benign	0.36

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: rs10496123; hg19: chr2-65309296;