rs76221156

Variant names:

• chr2-65077395-C-T
• rs76221156
• NM_015147.3:c.2008-473C>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.2008-473C>T 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 152,160 control chromosomes in the GnomAD database, including 1,091 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 (1091 hom., cov: 31)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 3 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=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 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.2008-473C>T		intron	N/A	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.2008-473C>T		intron	N/A	NP_001306029.1	Q76N32-1
	CEP68	NM_001410838.1		c.2008-473C>T		intron	N/A	NP_001397767.1	A0A994J4E5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.2008-473C>T		intron	N/A	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.1597-473C>T		intron	N/A	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000928054.1		c.2008-473C>T		intron	N/A	ENSP00000598113.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15605 AN: 152042 Hom.: 1092 Cov.: 31

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.103 AC: 15609 AN: 152160 Hom.: 1091 Cov.: 31 AF XY: 0.104 AC XY: 7741 AN XY: 74372

African (AFR) AF: 0.0235 AC: 975 AN: 41514

American (AMR) AF: 0.101 AC: 1542 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.102 AC: 527 AN: 5188

South Asian (SAS) AF: 0.195 AC: 939 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1518 AN: 10568

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

European-Non Finnish (NFE) AF: 0.132 AC: 9008 AN: 68000

Other (OTH) AF: 0.125 AC: 265 AN: 2114

Alfa AF: 0.122 Hom.: 173

Bravo AF: 0.0947

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		2.1
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: rs76221156; hg19: chr2-65304529;