Genetic Variant NM_015147.3:c.*2990G>C (chr2-65086624-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015147.3(CEP68):c.*2990G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,202 control chromosomes in the GnomAD database, including 1,104 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 ( 1103 hom., cov: 33)

Exomes 𝑓: 0.10 ( 1 hom. )

Consequence

CEP68
NM_015147.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

6 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:

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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=-0.52).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3 link	c.*2990G>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000377990.7	NP_055962.2	Q76N32-1
RAB1A	NM_004161.5 link	c.*1869C>G		downstream_gene_variant		ENST00000409784.8	NP_004152.1	P62820-1Q5U0I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7 link	c.*2990G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_015147.3	ENSP00000367229.2		Q76N32-1
RAB1A	ENST00000409784.8 link	c.*1869C>G		downstream_gene_variant		1	NM_004161.5	ENSP00000387286.3		P62820-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15695

AN:

152044

Hom.:

1104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

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:

0.144

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.100

AC:

AN:

Hom.:

Cov.:

AF XY:

0.107

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.105

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15699

AN:

152162

Hom.:

1103

Cov.:

AF XY:

0.105

AC XY:

7774

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0237

AC:

985

AN:

41534

American (AMR)

AF:

0.101

AC:

1540

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

690

AN:

3470

East Asian (EAS)

AF:

0.102

AC:

526

AN:

5180

South Asian (SAS)

AF:

0.195

AC:

940

AN:

4822

European-Finnish (FIN)

AF:

0.144

AC:

1520

AN:

10570

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9081

AN:

67994

Other (OTH)

AF:

0.127

AC:

268

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

713

1426

2140

2853

3566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.126

Hom.:

172

Bravo

AF:

0.0953

Asia WGS

AF:

0.182

AC:

630

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.1

(source)

DANN

Benign

0.56

PhyloP100

-0.032

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over