rs1894874

Variant names:

• chr2-65080245-T-C
• rs1894874
• NM_015147.3:c.2104+2281T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.2104+2281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 984,906 control chromosomes in the GnomAD database, including 7,755 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 (1102 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6653 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.2104+2281T>C		intron	N/A	NP_055962.2
	CEP68	NM_001319100.2		c.2104+2281T>C		intron	N/A	NP_001306029.1
	CEP68	NM_001410838.1		c.2105-31T>C		intron	N/A	NP_001397767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.2104+2281T>C		intron	N/A	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.1693+2281T>C		intron	N/A	ENSP00000260569.4
	CEP68	ENST00000704486.1		c.2104+2281T>C		intron	N/A	ENSP00000515914.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15716 AN: 152118 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.0241

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: 0.142

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.124 AC: 103306 AN: 832670 Hom.: 6653 Cov.: 30 AF XY: 0.124 AC XY: 47685 AN XY: 384526

African (AFR) AF: 0.0197 AC: 311 AN: 15780

American (AMR) AF: 0.111 AC: 109 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 1084 AN: 5150

East Asian (EAS) AF: 0.109 AC: 396 AN: 3630

South Asian (SAS) AF: 0.200 AC: 3283 AN: 16446

European-Finnish (FIN) AF: 0.156 AC: 43 AN: 276

Middle Eastern (MID) AF: 0.170 AC: 275 AN: 1620

European-Non Finnish (NFE) AF: 0.124 AC: 94074 AN: 761504

Other (OTH) AF: 0.137 AC: 3731 AN: 27280

GnomAD4 genome AF: 0.103 AC: 15720 AN: 152236 Hom.: 1102 Cov.: 32 AF XY: 0.104 AC XY: 7773 AN XY: 74414

African (AFR) AF: 0.0240 AC: 996 AN: 41558

American (AMR) AF: 0.101 AC: 1548 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3468

East Asian (EAS) AF: 0.101 AC: 525 AN: 5174

South Asian (SAS) AF: 0.195 AC: 943 AN: 4830

European-Finnish (FIN) AF: 0.142 AC: 1506 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9094 AN: 68018

Other (OTH) AF: 0.128 AC: 270 AN: 2110

Alfa AF: 0.123 Hom.: 174

Bravo AF: 0.0957

Asia WGS AF: 0.182 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		-0.22
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: rs1894874; hg19: chr2-65307379;