Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001330691.3(CEP78):c.84G>C(p.Ser28Ser) 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:4

Conservation

PhyloP100: -0.102

Publications

15 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330691.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP78	NM_001330691.3	MANE Select	c.84G>C	p.Ser28Ser	synonymous	Exon 1 of 17	NP_001317620.1
CEP78	NM_001098802.3		c.84G>C	p.Ser28Ser	synonymous	Exon 1 of 16	NP_001092272.1
CEP78	NM_001349838.2		c.84G>C	p.Ser28Ser	synonymous	Exon 1 of 16	NP_001336767.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CEP78	ENST00000643273.2	MANE Select	c.84G>C	p.Ser28Ser	synonymous	Exon 1 of 17	ENSP00000496423.2
CEP78	ENST00000376597.9	TSL:1	c.84G>C	p.Ser28Ser	synonymous	Exon 1 of 16	ENSP00000365782.4
CEP78	ENST00000643499.1		c.84G>C	p.Ser28Ser	synonymous	Exon 1 of 17	ENSP00000495962.1

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

GnomAD2 exomes

AF:

0.350

AC:

77528

AN:

221520

AF XY:

0.357

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 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

African (AFR)

AF:

0.158

AC:

5239

AN:

33262

American (AMR)

AF:

0.319

AC:

13672

AN:

42912

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

9955

AN:

25770

East Asian (EAS)

AF:

0.248

AC:

9710

AN:

39130

South Asian (SAS)

AF:

0.384

AC:

32307

AN:

84116

European-Finnish (FIN)

AF:

0.374

AC:

19274

AN:

51558

Middle Eastern (MID)

AF:

0.398

AC:

2287

AN:

5744

European-Non Finnish (NFE)

AF:

0.383

AC:

423090

AN:

1105368

Other (OTH)

AF:

0.364

AC:

21762

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19043

38086

57129

76172

95215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13108

26216

39324

52432

65540

<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:

0.318

AC:

48410

AN:

152092

Hom.:

8446

Cov.:

AF XY:

0.319

AC XY:

23688

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.171

AC:

7096

AN:

41528

American (AMR)

AF:

0.332

AC:

5078

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1328

AN:

3470

East Asian (EAS)

AF:

0.278

AC:

1434

AN:

5150

South Asian (SAS)

AF:

0.370

AC:

1783

AN:

4816

European-Finnish (FIN)

AF:

0.370

AC:

3915

AN:

10572

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26630

AN:

67954

Other (OTH)

AF:

0.340

AC:

719

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1671

3342

5013

6684

8355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.344

Hom.:

3015

Bravo

AF:

0.308

Asia WGS

AF:

0.291

AC:

1015

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.6

(source)

DANN

Benign

0.67

PhyloP100

-0.10

PromoterAI

-0.056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001330691.3:c.84G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over