Genetic Variant CEP164:p.Asn1373Asn (chr11-117410850-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014956.5(CEP164):c.4119C>T(p.Asn1373Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,612,948 control chromosomes in the GnomAD database, including 1,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 84 hom., cov: 32)

Exomes 𝑓: 0.034 ( 983 hom. )

Consequence

CEP164
NM_014956.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.294

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-117410850-C-T is Benign according to our data. Variant chr11-117410850-C-T is described in ClinVar as [Benign]. Clinvar id is 260489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-117410850-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.294 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0259 (3937/152266) while in subpopulation NFE AF= 0.0389 (2647/68004). AF 95% confidence interval is 0.0377. There are 84 homozygotes in gnomad4. There are 1957 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP164	NM_014956.5 link	c.4119C>T	p.Asn1373Asn	synonymous_variant	Exon 31 of 33	ENST00000278935.8	NP_055771.4	Q9UPV0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8 link	c.4119C>T	p.Asn1373Asn	synonymous_variant	Exon 31 of 33	1	NM_014956.5	ENSP00000278935.3		Q9UPV0-1

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3935

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00589

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.0522

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0288

AC:

7176

AN:

249230

Hom.:

152

AF XY:

0.0299

AC XY:

4036

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00708

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.0321

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0301

Gnomad FIN exome

AF:

0.0499

Gnomad NFE exome

AF:

0.0375

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0343

AC:

50087

AN:

1460682

Hom.:

983

Cov.:

AF XY:

0.0345

AC XY:

25036

AN XY:

726462

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.0486

Gnomad4 NFE exome

AF:

0.0374

Gnomad4 OTH exome

AF:

0.0289

GnomAD4 genome

AF:

0.0259

AC:

3937

AN:

152266

Hom.:

Cov.:

AF XY:

0.0263

AC XY:

1957

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00587

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.0522

Gnomad4 NFE

AF:

0.0389

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0265

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0352

EpiControl

AF:

0.0354

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nephronophthisis 15

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.40

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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