NM_015147.3:c.2105-374G>A

Variant names:

• chr2-65082162-G-A
• rs10496123
• NM_015147.3:c.2105-374G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

RAB1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015147.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.2105-374G>A		intron	N/A	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.2105-374G>A		intron	N/A	NP_001306029.1	Q76N32-1
	CEP68	NM_001319101.2		c.1694-374G>A		intron	N/A	NP_001306030.1	Q76N32-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.2105-374G>A		intron	N/A	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.1694-374G>A		intron	N/A	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000928054.1		c.2105-12G>A		intron	N/A	ENSP00000598113.1

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

African (AFR) AF: 0.0659 AC: 2740 AN: 41568

American (AMR) AF: 0.218 AC: 3334 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5174

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4828

European-Finnish (FIN) AF: 0.259 AC: 2739 AN: 10566

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19169 AN: 67980

Other (OTH) AF: 0.212 AC: 447 AN: 2110

Alfa AF: 0.246 Hom.: 12068

Bravo AF: 0.201

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10496123; hg19: chr2-65309296;