rs114396665

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014956.5(CEP164):c.1480C>A(p.Pro494Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,603,380 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P494P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0065 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 7 hom. )

Consequence

CEP164
NM_014956.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0460

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:

CEP164 (HGNC:):

CEP164 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003118813).

BP6

Variant 11-117381771-C-A is Benign according to our data. Variant chr11-117381771-C-A is described in ClinVar as [Benign]. Clinvar id is 540297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117381771-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0065 (990/152240) while in subpopulation AFR AF= 0.0227 (944/41524). AF 95% confidence interval is 0.0215. There are 15 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP164	NM_014956.5 linkuse as main transcript	c.1480C>A	p.Pro494Thr	missense_variant	13/33	ENST00000278935.8	NP_055771.4	Q9UPV0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CEP164	ENST00000278935.8 linkuse as main transcript	c.1480C>A	p.Pro494Thr	missense_variant	13/33	1	NM_014956.5	ENSP00000278935.3	Q9UPV0-1
CEP164	ENST00000533675.5 linkuse as main transcript	n.1735C>A		non_coding_transcript_exon_variant	9/27	2
CEP164	ENST00000533706.5 linkuse as main transcript	n.804C>A		non_coding_transcript_exon_variant	6/27	5

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00153

AC:

341

AN:

222628

Hom.:

AF XY:

0.00119

AC XY:

144

AN XY:

121308

show subpopulations

Gnomad AFR exome

AF:

0.0231

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000726

GnomAD4 exome

AF:

0.000676

AC:

981

AN:

1451140

Hom.:

Cov.:

AF XY:

0.000583

AC XY:

420

AN XY:

720824

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000950

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00650

AC:

990

AN:

152240

Hom.:

Cov.:

AF XY:

0.00648

AC XY:

482

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00740

ExAC

AF:

0.00184

AC:

222

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CEP164-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 05, 2024

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

Nephronophthisis 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.0

REVEL

Benign

0.090

Sift

Uncertain

0.016

Sift4G

Benign

0.14

Polyphen

0.98

Vest4

0.25

MVP

0.48

MPC

0.40

ClinPred

0.018

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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