rs490262

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014956.5(CEP164):c.281G>A(p.Ser94Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,052 control chromosomes in the GnomAD database, including 34,334 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3700 hom., cov: 30)

Exomes 𝑓: 0.20 ( 30634 hom. )

Consequence

CEP164
NM_014956.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.937

Variant links:

Genes affected

CEP164 (HGNC:29182): (centrosomal protein 164) This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CEP164 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023169518).

BP6

Variant 11-117351876-G-A is Benign according to our data. Variant chr11-117351876-G-A is described in ClinVar as [Benign]. Clinvar id is 260481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117351876-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP164	NM_014956.5 link	c.281G>A	p.Ser94Asn	missense_variant	Exon 5 of 33	ENST00000278935.8	NP_055771.4	Q9UPV0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8 link	c.281G>A	p.Ser94Asn	missense_variant	Exon 5 of 33	1	NM_014956.5	ENSP00000278935.3		Q9UPV0-1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32711

AN:

151178

Hom.:

3690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.211

AC:

53130

AN:

251368

Hom.:

6079

AF XY:

0.209

AC XY:

28334

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.190

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.201

AC:

294485

AN:

1461762

Hom.:

30634

Cov.:

AF XY:

0.202

AC XY:

146847

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.216

AC:

32754

AN:

151290

Hom.:

3700

Cov.:

AF XY:

0.213

AC XY:

15735

AN XY:

73882

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.209

Alfa

AF:

0.198

Hom.:

7519

Bravo

AF:

0.229

TwinsUK

AF:

0.203

AC:

753

ALSPAC

AF:

0.188

AC:

724

ESP6500AA

AF:

0.275

AC:

1211

ESP6500EA

AF:

0.200

AC:

1718

ExAC

AF:

0.209

AC:

25382

Asia WGS

AF:

0.193

AC:

673

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.190

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nephronophthisis 15

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.5

DANN

Benign

0.51

DEOGEN2

Benign

0.0048

.;T;T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.045

T;T;T;T;.;T

MetaRNN

Benign

0.0023

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.5

.;.;N;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

1.2

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.80

T;T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T;T

Polyphen

0.0

.;.;B;.;.;.

Vest4

0.044

MPC

0.095

ClinPred

0.0042

GERP RS

3.7

Varity_R

0.033

gMVP

0.046

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over