rs6741255

Variant names:

• chr2-65079771-C-T
• rs6741255
• NM_015147.3:c.2104+1807C>T

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+1807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,156 control chromosomes in the GnomAD database, including 32,737 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 0.65 (32737 hom., cov: 33)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 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+1807C>T		intron	N/A	NP_055962.2
	CEP68	NM_001319100.2		c.2104+1807C>T		intron	N/A	NP_001306029.1
	CEP68	NM_001410838.1		c.2105-505C>T		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+1807C>T		intron	N/A	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.1693+1807C>T		intron	N/A	ENSP00000260569.4
	CEP68	ENST00000704486.1		c.2104+1807C>T		intron	N/A	ENSP00000515914.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99343 AN: 152038 Hom.: 32723 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.653 AC: 99392 AN: 152156 Hom.: 32737 Cov.: 33 AF XY: 0.654 AC XY: 48643 AN XY: 74392

African (AFR) AF: 0.585 AC: 24296 AN: 41502

American (AMR) AF: 0.671 AC: 10251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1964 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3435 AN: 5174

South Asian (SAS) AF: 0.615 AC: 2965 AN: 4820

European-Finnish (FIN) AF: 0.714 AC: 7554 AN: 10582

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46765 AN: 68006

Other (OTH) AF: 0.621 AC: 1310 AN: 2110

Alfa AF: 0.666 Hom.: 4348

Bravo AF: 0.648

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.43
PhyloP100		-0.83
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: rs6741255; hg19: chr2-65306905;