dbSNP rs12611491: CEP68:p.Arg27Gly (chr2-65069523-A-G) – 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.79A>G(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,587,312 control chromosomes in the GnomAD database, including 1,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.022 ( 206 hom., cov: 32)

Exomes 𝑓: 0.016 ( 1481 hom. )

Consequence

CEP68
NM_015147.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.820

Publications

11 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:

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 (MetaRNN=0.0035800934).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3 link	c.79A>G	p.Arg27Gly	missense_variant	Exon 2 of 7	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7 link	c.79A>G	p.Arg27Gly	missense_variant	Exon 2 of 7	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3356

AN:

152154

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00905

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0692

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.0164

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00532

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0416

AC:

9693

AN:

233006

AF XY:

0.0363

show subpopulations

Gnomad AFR exome

AF:

0.00808

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0164

AC:

23545

AN:

1435040

Hom.:

1481

Cov.:

AF XY:

0.0159

AC XY:

11275

AN XY:

711082

show subpopulations

African (AFR)

AF:

0.00723

AC:

237

AN:

32788

American (AMR)

AF:

0.115

AC:

4823

AN:

41808

Ashkenazi Jewish (ASJ)

AF:

0.0165

AC:

395

AN:

23928

East Asian (EAS)

AF:

0.233

AC:

9192

AN:

39370

South Asian (SAS)

AF:

0.0141

AC:

1179

AN:

83358

European-Finnish (FIN)

AF:

0.0172

AC:

900

AN:

52344

Middle Eastern (MID)

AF:

0.00802

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00506

AC:

5546

AN:

1096830

Other (OTH)

AF:

0.0208

AC:

1228

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1223

2445

3668

4890

6113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.0220

AC:

3357

AN:

152272

Hom.:

206

Cov.:

AF XY:

0.0243

AC XY:

1809

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00902

AC:

375

AN:

41568

American (AMR)

AF:

0.0692

AC:

1058

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3470

East Asian (EAS)

AF:

0.226

AC:

1170

AN:

5168

South Asian (SAS)

AF:

0.0212

AC:

102

AN:

4820

European-Finnish (FIN)

AF:

0.0164

AC:

174

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00532

AC:

362

AN:

68006

Other (OTH)

AF:

0.0274

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

151

302

454

605

756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0161

Hom.:

247

Bravo

AF:

0.0278

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.0356

AC:

4323

Asia WGS

AF:

0.118

AC:

410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.18

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0022

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.63

N;N

PhyloP100

-0.82

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.014

Sift

Benign

0.15

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0

B;B

Vest4

0.029

MPC

0.052

ClinPred

0.00041

GERP RS

-3.7

Varity_R

0.13

gMVP

0.074

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