Variant 11-117361836-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014956.5(CEP164):c.395C>G(p.Ala132Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,614,200 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A132S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0058 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 7 hom. )

Consequence

CEP164
NM_014956.5 missense, splice_region

Scores

Splicing: ADA: 0.0001332

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.23

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005328566).

BP6

Variant 11-117361836-C-G is Benign according to our data. Variant chr11-117361836-C-G is described in ClinVar as [Benign]. Clinvar id is 540296.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-117361836-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00578 (880/152332) while in subpopulation AFR AF= 0.0202 (839/41578). AF 95% confidence interval is 0.019. There are 11 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP164	NM_014956.5 linkuse as main transcript	c.395C>G	p.Ala132Gly	missense_variant, splice_region_variant	6/33	ENST00000278935.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP164	ENST00000278935.8 linkuse as main transcript	c.395C>G	p.Ala132Gly	missense_variant, splice_region_variant	6/33	1	NM_014956.5	P1	Q9UPV0-1

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

878

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

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:

0.0000441

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00150

AC:

377

AN:

251442

Hom.:

AF XY:

0.00111

AC XY:

151

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000605

AC:

884

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

375

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00578

AC:

880

AN:

152332

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

437

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0202

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.000514

Hom.:

Bravo

AF:

0.00660

ESP6500AA

AF:

0.0189

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00171

AC:

208

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephronophthisis 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.58

T;T;T

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.97

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.34

.;B;.

Vest4

0.23

MVP

0.52

MPC

0.22

ClinPred

0.0059

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.030

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