rs10867166

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001330691.3(CEP78):c.84G>C(p.Ser28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,599,716 control chromosomes in the GnomAD database, including 109,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8446 hom., cov: 32)

Exomes 𝑓: 0.37 ( 101240 hom. )

Consequence

CEP78
NM_001330691.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.102

Variant links:

Genes affected

CEP78 (HGNC:25740): (centrosomal protein 78) This gene encodes a centrosomal protein that is both required for the regulation of centrosome-related events during the cell cycle, and required for ciliogenesis. The encoded protein has an N-terminal leucine-rich repeat (LRR) domain with six consecutive LRR repeats, and a C-terminal coiled-coil domain. It interacts with the N-terminal catalytic domain of polo-like kinase 4 (PLK4) and colocalizes with PLK4 to the distal end of the centriole. Naturally occurring mutations in this gene cause defects in primary cilia that result in retinal degeneration and sensorineural hearing loss which are associated with cone-rod degeneration disease as well as Usher syndrome. Low expression of this gene is associated with poor prognosis of colorectal cancer patients. [provided by RefSeq, Mar 2017]

CEP78 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=-0.54).

BP6

Variant 9-78236434-G-C is Benign according to our data. Variant chr9-78236434-G-C is described in ClinVar as [Benign]. Clinvar id is 517538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.102 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP78	NM_001330691.3 linkuse as main transcript	c.84G>C	p.Ser28=	synonymous_variant	1/17	ENST00000643273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP78	ENST00000643273.2 linkuse as main transcript	c.84G>C	p.Ser28=	synonymous_variant	1/17		NM_001330691.3	P4	Q5JTW2-3

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48386

AN:

151974

Hom.:

8445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.350

AC:

77528

AN:

221520

Hom.:

13869

AF XY:

0.357

AC XY:

43131

AN XY:

120828

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.381

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.371

AC:

537296

AN:

1447624

Hom.:

101240

Cov.:

AF XY:

0.373

AC XY:

267954

AN XY:

718684

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.386

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.364

GnomAD4 genome

AF:

0.318

AC:

48410

AN:

152092

Hom.:

8446

Cov.:

AF XY:

0.319

AC XY:

23688

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.392

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.344

Hom.:

3015

Bravo

AF:

0.308

Asia WGS

AF:

0.291

AC:

1015

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Ser28Ser in exon 1 of CEP78: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 45.32% (19356/42712) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs10867166). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

Cadd

Benign

9.6

Dann

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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