Variant chr2-65071523-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015147.3(CEP68):c.427A>G(p.Ile143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,124 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 834 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 760 hom. )

Consequence

CEP68
NM_015147.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036167204).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3 link	c.427A>G	p.Ile143Val	missense_variant	3/7	ENST00000377990.7	NP_055962.2	Q76N32-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7 link	c.427A>G	p.Ile143Val	missense_variant	3/7	1	NM_015147.3	ENSP00000367229.2		Q76N32-1

Frequencies

GnomAD3 genomes

AF:

0.0576

AC:

8726

AN:

151522

Hom.:

829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000833

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000767

Gnomad OTH

AF:

0.0480

GnomAD3 exomes

AF:

0.0153

AC:

3835

AN:

251458

Hom.:

395

AF XY:

0.0113

AC XY:

1541

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.00920

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00584

AC:

8537

AN:

1461484

Hom.:

760

Cov.:

AF XY:

0.00511

AC XY:

3713

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000358

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0578

AC:

8765

AN:

151640

Hom.:

834

Cov.:

AF XY:

0.0562

AC XY:

4169

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0228

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000767

Gnomad4 OTH

AF:

0.0475

Alfa

AF:

0.0110

Hom.:

202

Bravo

AF:

0.0650

ESP6500AA

AF:

0.194

AC:

853

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0190

AC:

2301

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.011

DANN

Benign

0.54

DEOGEN2

Benign

0.0014

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.14

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.044

Sift

Benign

0.80

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.013

MPC

0.040

ClinPred

0.0012

GERP RS

-0.64

Varity_R

0.044

gMVP

0.063

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over