rs1057650

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

cone-rod dystrophy and hearing loss
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P
cone-rod dystrophy and hearing loss 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
Usher syndrome type 3
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP78 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CEP78	NM_001330691.3 link	c.1542C>T	p.Ile514Ile	synonymous_variant	Exon 13 of 17	ENST00000643273.2	NP_001317620.1	Q5JTW2-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2 link	c.1542C>T	p.Ile514Ile	synonymous_variant	Exon 13 of 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

GnomAD2 exomes

AF:

0.0781

AC:

19221

AN:

246130

AF XY:

0.0802

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 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

African (AFR)

AF:

0.136

AC:

4505

AN:

33154

American (AMR)

AF:

0.0663

AC:

2935

AN:

44292

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

2275

AN:

26036

East Asian (EAS)

AF:

0.00843

AC:

332

AN:

39392

South Asian (SAS)

AF:

0.0988

AC:

8489

AN:

85962

European-Finnish (FIN)

AF:

0.0692

AC:

3688

AN:

53326

Middle Eastern (MID)

AF:

0.117

AC:

672

AN:

5758

European-Non Finnish (NFE)

AF:

0.0834

AC:

92535

AN:

1109786

Other (OTH)

AF:

0.0847

AC:

5096

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5500

11001

16501

22002

27502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3518

7036

10554

14072

17590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0939

AC:

14284

AN:

152070

Hom.:

766

Cov.:

AF XY:

0.0911

AC XY:

6771

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.137

AC:

5676

AN:

41474

American (AMR)

AF:

0.0767

AC:

1171

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0890

AC:

309

AN:

3470

East Asian (EAS)

AF:

0.0122

AC:

AN:

5182

South Asian (SAS)

AF:

0.0937

AC:

451

AN:

4814

European-Finnish (FIN)

AF:

0.0660

AC:

697

AN:

10562

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0827

AC:

5620

AN:

67978

Other (OTH)

AF:

0.0882

AC:

186

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

645

1290

1935

2580

3225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0858

Hom.:

1095

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

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.71

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over