chr9-78243456-T-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001330691.3(CEP78):​c.604-6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,608,776 control chromosomes in the GnomAD database, including 132 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 0.017 ( 64 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 68 hom. )

Consequence

CEP78
NM_001330691.3 splice_region, intron

Scores

2
Splicing: ADA: 0.5007
2

Clinical Significance

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

Conservation

PhyloP100: 1.50

Publications

3 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 9-78243456-T-G is Benign according to our data. Variant chr9-78243456-T-G is described in ClinVar as [Benign]. Clinvar id is 517537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP78NM_001330691.3 linkc.604-6T>G splice_region_variant, intron_variant Intron 4 of 16 ENST00000643273.2 NP_001317620.1 Q5JTW2-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP78ENST00000643273.2 linkc.604-6T>G splice_region_variant, intron_variant Intron 4 of 16 NM_001330691.3 ENSP00000496423.2 Q5JTW2-3

Frequencies

GnomAD3 genomes
AF:
0.0172
AC:
2621
AN:
152188
Hom.:
64
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0592
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00890
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0110
GnomAD2 exomes
AF:
0.00478
AC:
1167
AN:
244158
AF XY:
0.00358
show subpopulations
Gnomad AFR exome
AF:
0.0658
Gnomad AMR exome
AF:
0.00315
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000270
Gnomad OTH exome
AF:
0.00220
GnomAD4 exome
AF:
0.00178
AC:
2586
AN:
1456470
Hom.:
68
Cov.:
29
AF XY:
0.00157
AC XY:
1136
AN XY:
724526
show subpopulations
African (AFR)
AF:
0.0598
AC:
1983
AN:
33138
American (AMR)
AF:
0.00417
AC:
182
AN:
43658
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25818
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39612
South Asian (SAS)
AF:
0.000258
AC:
22
AN:
85234
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53340
Middle Eastern (MID)
AF:
0.00488
AC:
28
AN:
5740
European-Non Finnish (NFE)
AF:
0.000106
AC:
118
AN:
1109804
Other (OTH)
AF:
0.00421
AC:
253
AN:
60126
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
113
227
340
454
567
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
70
140
210
280
350
<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:
0.0173
AC:
2628
AN:
152306
Hom.:
64
Cov.:
32
AF XY:
0.0165
AC XY:
1228
AN XY:
74476
show subpopulations
African (AFR)
AF:
0.0592
AC:
2459
AN:
41546
American (AMR)
AF:
0.00882
AC:
135
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000118
AC:
8
AN:
68026
Other (OTH)
AF:
0.0109
AC:
23
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
126
252
378
504
630
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
28
56
84
112
140
<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:
0.00894
Hom.:
22
Bravo
AF:
0.0200
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.000383
EpiControl
AF:
0.000297

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
May 05, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
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

- -

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

c.604-6T>G in intron 4 of CEP78: This variant is not expected to have clinical s ignificance because it has been identified in 6.45% (629/9758) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs17064247). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
13
DANN
Benign
0.91
PhyloP100
1.5
Mutation Taster
=94/6
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.50
dbscSNV1_RF
Benign
0.70
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17064247; hg19: chr9-80858372; API