rs117083334

Positions:

chr11-117381721-A-G

Variant summary

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

The ENST00000278935.8(CEP164):c.1430A>G(p.His477Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 1,609,834 control chromosomes in the GnomAD database, including 1,055 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 (★★). Synonymous variant affecting the same amino acid position (i.e. H477H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.025 ( 53 hom., cov: 32)

Exomes 𝑓: 0.034 ( 1002 hom. )

Consequence

CEP164
ENST00000278935.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.32

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=0.0025341213).

BP6

Variant 11-117381721-A-G is Benign according to our data. Variant chr11-117381721-A-G is described in ClinVar as [Benign]. Clinvar id is 194251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117381721-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3804/152240) while in subpopulation NFE AF= 0.0371 (2526/68008). AF 95% confidence interval is 0.0359. There are 53 homozygotes in gnomad4. There are 1752 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP164	NM_014956.5 linkuse as main transcript	c.1430A>G	p.His477Arg	missense_variant	13/33	ENST00000278935.8	NP_055771.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8 linkuse as main transcript	c.1430A>G	p.His477Arg	missense_variant	13/33	1	NM_014956.5	ENSP00000278935	P1	Q9UPV0-1
CEP164	ENST00000533675.5 linkuse as main transcript	n.1685A>G		non_coding_transcript_exon_variant	9/27	2
CEP164	ENST00000533706.5 linkuse as main transcript	n.754A>G		non_coding_transcript_exon_variant	6/27	5

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3805

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00741

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0241

AC:

5735

AN:

237776

Hom.:

106

AF XY:

0.0249

AC XY:

3228

AN XY:

129496

show subpopulations

Gnomad AFR exome

AF:

0.00612

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0495

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0102

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0339

AC:

49368

AN:

1457594

Hom.:

1002

Cov.:

AF XY:

0.0335

AC XY:

24248

AN XY:

724724

show subpopulations

Gnomad4 AFR exome

AF:

0.00605

Gnomad4 AMR exome

AF:

0.0207

Gnomad4 ASJ exome

AF:

0.0459

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0384

Gnomad4 OTH exome

AF:

0.0340

GnomAD4 genome

AF:

0.0250

AC:

3804

AN:

152240

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1752

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00739

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00726

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.0371

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0335

Hom.:

Bravo

AF:

0.0252

TwinsUK

AF:

0.0396

AC:

147

ALSPAC

AF:

0.0384

AC:

148

ESP6500AA

AF:

0.00659

AC:

ESP6500EA

AF:

0.0337

AC:

289

ExAC

AF:

0.0225

AC:

2727

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 01, 2015	- -

Nephronophthisis 15

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

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

0.064

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.0020

DANN

Benign

0.26

DEOGEN2

Benign

0.0045

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.23

REVEL

Benign

0.020

Sift

Benign

0.54

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.020

MPC

0.13

ClinPred

0.00020

GERP RS

-7.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.078

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