11-117381729-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014956.5(CEP164):c.1438C>T(p.Arg480Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,609,866 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R480Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 2 hom. )

Consequence

CEP164
NM_014956.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.368

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
nephronophthisis 15
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, G2P
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP164 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047689974).

BP6

Variant 11-117381729-C-T is Benign according to our data. Variant chr11-117381729-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 285113.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000742 (113/152320) while in subpopulation AFR AF = 0.00241 (100/41566). AF 95% confidence interval is 0.00202. There are 0 homozygotes in GnomAd4. There are 57 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP164	NM_014956.5 link	c.1438C>T	p.Arg480Trp	missense_variant	Exon 13 of 33	ENST00000278935.8	NP_055771.4	Q9UPV0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP164	ENST00000278935.8 link	c.1438C>T	p.Arg480Trp	missense_variant	Exon 13 of 33	1	NM_014956.5	ENSP00000278935.3	Q9UPV0-1
CEP164	ENST00000533675.5 link	n.1693C>T		non_coding_transcript_exon_variant	Exon 9 of 27	2
CEP164	ENST00000533706.5 link	n.762C>T		non_coding_transcript_exon_variant	Exon 6 of 27	5

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000160

AC:

AN:

237596

AF XY:

0.000101

show subpopulations

Gnomad AFR exome

AF:

0.00192

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000471

Gnomad OTH exome

AF:

0.000520

GnomAD4 exome

AF:

0.000139

AC:

203

AN:

1457546

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

724734

show subpopulations

African (AFR)

AF:

0.00297

AC:

AN:

33378

American (AMR)

AF:

0.000248

AC:

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25984

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39602

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52962

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

1110288

Other (OTH)

AF:

0.000349

AC:

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000742

AC:

113

AN:

152320

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00241

AC:

100

AN:

41566

American (AMR)

AF:

0.000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000290

Hom.:

Bravo

AF:

0.000808

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 21, 2015

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CEP164-related disorder

Benign:1

Aug 25, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Nephronophthisis 15

Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0057

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.71

M_CAP

Benign

0.024

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-0.37

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.3

REVEL

Benign

0.036

Sift

Benign

0.17

Sift4G

Benign

0.13

Polyphen

0.022

Vest4

0.21

MVP

0.20

MPC

0.11

ClinPred

0.011

GERP RS

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.15

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over