11-117397168-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014956.5(CEP164):c.3356A>G(p.Gln1119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,614,028 control chromosomes in the GnomAD database, including 218,664 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1119W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.51 ( 20023 hom., cov: 34)

Exomes 𝑓: 0.52 ( 198641 hom. )

Consequence

CEP164
NM_014956.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.631

Publications

41 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5159534E-5).

BP6

Variant 11-117397168-A-G is Benign according to our data. Variant chr11-117397168-A-G is described in ClinVar as Benign. ClinVar VariationId is 260485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP164	NM_014956.5	MANE Select	c.3356A>G	p.Gln1119Arg	missense	Exon 27 of 33	NP_055771.4
CEP164	NM_001440949.1		c.3362A>G	p.Gln1121Arg	missense	Exon 27 of 33	NP_001427878.1
CEP164	NM_001440950.1		c.3356A>G	p.Gln1119Arg	missense	Exon 27 of 33	NP_001427879.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP164	ENST00000278935.8	TSL:1 MANE Select	c.3356A>G	p.Gln1119Arg	missense	Exon 27 of 33	ENSP00000278935.3
CEP164	ENST00000533223.1	TSL:1	n.4238A>G		non_coding_transcript_exon	Exon 13 of 16
CEP164	ENST00000533675.5	TSL:2	n.3583A>G		non_coding_transcript_exon	Exon 21 of 27

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77337

AN:

152088

Hom.:

20005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.472

AC:

118728

AN:

251282

AF XY:

0.480

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.531

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.518

AC:

756792

AN:

1461822

Hom.:

198641

Cov.:

AF XY:

0.518

AC XY:

376409

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.531

AC:

17783

AN:

33480

American (AMR)

AF:

0.260

AC:

11645

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

12806

AN:

26132

East Asian (EAS)

AF:

0.380

AC:

15093

AN:

39696

South Asian (SAS)

AF:

0.472

AC:

40672

AN:

86250

European-Finnish (FIN)

AF:

0.526

AC:

28069

AN:

53386

Middle Eastern (MID)

AF:

0.498

AC:

2873

AN:

5768

European-Non Finnish (NFE)

AF:

0.537

AC:

597557

AN:

1111994

Other (OTH)

AF:

0.502

AC:

30294

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

21260

42519

63779

85038

106298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16780

33560

50340

67120

83900

<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:

0.508

AC:

77390

AN:

152206

Hom.:

20023

Cov.:

AF XY:

0.504

AC XY:

37514

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.524

AC:

21734

AN:

41510

American (AMR)

AF:

0.350

AC:

5352

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1761

AN:

3472

East Asian (EAS)

AF:

0.350

AC:

1812

AN:

5184

South Asian (SAS)

AF:

0.468

AC:

2262

AN:

4830

European-Finnish (FIN)

AF:

0.522

AC:

5532

AN:

10602

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.546

AC:

37145

AN:

67988

Other (OTH)

AF:

0.514

AC:

1087

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2065

4129

6194

8258

10323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.519

Hom.:

19880

Bravo

AF:

0.494

TwinsUK

AF:

0.530

AC:

1964

ALSPAC

AF:

0.542

AC:

2090

ESP6500AA

AF:

0.512

AC:

2256

ESP6500EA

AF:

0.545

AC:

4681

ExAC

AF:

0.485

AC:

58878

Asia WGS

AF:

0.425

AC:

1479

AN:

3478

EpiCase

AF:

0.546

EpiControl

AF:

0.538

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephronophthisis 15 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

(source)

DANN

Benign

0.094

DEOGEN2

Benign

0.0091

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.42

MetaRNN

Benign

0.000015

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.45

PhyloP100

-0.63

PrimateAI

Benign

0.23

PROVEAN

Benign

1.2

REVEL

Benign

0.0070

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.068

MPC

0.11

ClinPred

0.0019

GERP RS

-1.7

Varity_R

0.015

gMVP

0.028

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over