Variant rs1057650 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001330691.3(CEP78):c.1542C>T(p.Ile514Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 1,609,952 control chromosomes in the GnomAD database, including 6,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 766 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5363 hom. )

Consequence

CEP78
NM_001330691.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.545

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:

CEP78 (HGNC:):

CEP78 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 9-78264233-C-T is Benign according to our data. Variant chr9-78264233-C-T is described in ClinVar as [Benign]. Clinvar id is 517541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.545 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP78	NM_001330691.3 linkuse as main transcript	c.1542C>T	p.Ile514Ile	synonymous_variant	13/17	ENST00000643273.2	NP_001317620.1	Q5JTW2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2 linkuse as main transcript	c.1542C>T	p.Ile514Ile	synonymous_variant	13/17		NM_001330691.3	ENSP00000496423.2		Q5JTW2-3

Frequencies

GnomAD3 genomes

AF:

0.0939

AC:

14273

AN:

151952

Hom.:

764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.0890

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.0942

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0827

Gnomad OTH

AF:

0.0896

GnomAD3 exomes

AF:

0.0781

AC:

19221

AN:

246130

Hom.:

854

AF XY:

0.0802

AC XY:

10720

AN XY:

133680

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.0635

Gnomad ASJ exome

AF:

0.0873

Gnomad EAS exome

AF:

0.00723

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0691

Gnomad NFE exome

AF:

0.0805

Gnomad OTH exome

AF:

0.0838

GnomAD4 exome

AF:

0.0827

AC:

120527

AN:

1457882

Hom.:

5363

Cov.:

AF XY:

0.0833

AC XY:

60425

AN XY:

725350

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0663

Gnomad4 ASJ exome

AF:

0.0874

Gnomad4 EAS exome

AF:

0.00843

Gnomad4 SAS exome

AF:

0.0988

Gnomad4 FIN exome

AF:

0.0692

Gnomad4 NFE exome

AF:

0.0834

Gnomad4 OTH exome

AF:

0.0847

GnomAD4 genome

AF:

0.0939

AC:

14284

AN:

152070

Hom.:

766

Cov.:

AF XY:

0.0911

AC XY:

6771

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.0767

Gnomad4 ASJ

AF:

0.0890

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.0937

Gnomad4 FIN

AF:

0.0660

Gnomad4 NFE

AF:

0.0827

Gnomad4 OTH

AF:

0.0882

Alfa

AF:

0.0853

Hom.:

966

Bravo

AF:

0.0966

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

p.Ile515Ile in exon 13 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 13.43% (1308/9742) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs1057650). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

7.9

DANN

Benign

0.71

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