rs13292584

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330691.3(CEP78):c.253+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,523,010 control chromosomes in the GnomAD database, including 104,533 homozygotes. In-silico tool predicts 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 (★★).

Frequency

Genomes: 𝑓 0.32 ( 8440 hom., cov: 32)

Exomes 𝑓: 0.37 ( 96093 hom. )

Consequence

CEP78
NM_001330691.3 splice_region, intron

Scores

Splicing: ADA: 0.004088

Clinical Significance

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

Conservation

PhyloP100: 1.36

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-78236611-G-A is Benign according to our data. Variant chr9-78236611-G-A is described in ClinVar as [Benign]. Clinvar id is 517539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.253+8G>A		splice_region_variant, intron_variant		ENST00000643273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP78	ENST00000643273.2 linkuse as main transcript	c.253+8G>A		splice_region_variant, intron_variant			NM_001330691.3	P4	Q5JTW2-3

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48371

AN:

151976

Hom.:

8440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.350

AC:

60191

AN:

171744

Hom.:

10796

AF XY:

0.359

AC XY:

32910

AN XY:

91576

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.267

Gnomad SAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.372

AC:

509650

AN:

1370916

Hom.:

96093

Cov.:

AF XY:

0.373

AC XY:

251092

AN XY:

672656

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.321

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.375

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.318

AC:

48392

AN:

152094

Hom.:

8440

Cov.:

AF XY:

0.318

AC XY:

23666

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.392

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.343

Hom.:

2693

Bravo

AF:

0.308

Asia WGS

AF:

0.291

AC:

1014

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	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

c.253+8G>A in intron 1 of CEP78: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 41.93% (3473/8282) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs13292584). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

Cadd

Benign

Dann

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0041

dbscSNV1_RF

Benign

0.0080

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