Genetic Variant CEP68:n.2238C>T (chr2-65073618-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000537589.1(CEP68):n.2238C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 161,052 control chromosomes in the GnomAD database, including 2,767 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 0.17 ( 2612 hom., cov: 32)

Exomes 𝑓: 0.18 ( 155 hom. )

Consequence

CEP68
ENST00000537589.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

4 publications found

Variant links:

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]

CEP68 links:

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

RAB1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3 link	c.1884+638C>T		intron_variant	Intron 3 of 6	ENST00000377990.7	NP_055962.2	Q76N32-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7 link	c.1884+638C>T		intron_variant	Intron 3 of 6	1	NM_015147.3	ENSP00000367229.2		Q76N32-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25473

AN:

152136

Hom.:

2602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.175

AC:

1541

AN:

8798

Hom.:

155

Cov.:

AF XY:

0.170

AC XY:

767

AN XY:

4512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.191

AC:

335

AN:

1752

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

AN:

East Asian (EAS)

AF:

0.274

AC:

AN:

230

South Asian (SAS)

AF:

0.226

AC:

202

AN:

894

European-Finnish (FIN)

AF:

0.0923

AC:

AN:

130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.161

AC:

861

AN:

5332

Other (OTH)

AF:

0.150

AC:

AN:

366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

122

184

245

306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25499

AN:

152254

Hom.:

2612

Cov.:

AF XY:

0.170

AC XY:

12672

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0699

AC:

2905

AN:

41572

American (AMR)

AF:

0.210

AC:

3218

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1055

AN:

3472

East Asian (EAS)

AF:

0.334

AC:

1730

AN:

5178

South Asian (SAS)

AF:

0.288

AC:

1392

AN:

4826

European-Finnish (FIN)

AF:

0.178

AC:

1887

AN:

10600

Middle Eastern (MID)

AF:

0.277

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.186

AC:

12617

AN:

67996

Other (OTH)

AF:

0.211

AC:

446

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1067

2134

3201

4268

5335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.178

Hom.:

440

Bravo

AF:

0.166

Asia WGS

AF:

0.366

AC:

1270

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

0.21

(source)

DANN

Benign

0.79

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over