9-78236227-C-T

Position:

• chr9-78236227-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330691.3(CEP78):​c.-124C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 824,166 control chromosomes in the GnomAD database, including 1,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (410 hom., cov: 33)
  • Exomes 𝑓: 0.041 (901 hom.)
• Consequence: CEP78 NM_001330691.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-78236227-C-T is Benign according to our data. Variant chr9-78236227-C-T is described in ClinVar as [Benign]. Clinvar id is 1264250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP78	NM_001330691.3	c.-124C>T		5_prime_UTR_variant	1/17	ENST00000643273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP78	ENST00000643273.2	c.-124C>T		5_prime_UTR_variant	1/17		NM_001330691.3	P4

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9598 AN: 152088 Hom.: 405 Cov.: 33

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0584

GnomAD4 exome AF: 0.0413 AC: 27748 AN: 671962 Hom.: 901 Cov.: 9 AF XY: 0.0413 AC XY: 14302 AN XY: 346556

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0376

Gnomad4 EAS exome AF: 0.0799

Gnomad4 SAS exome AF: 0.0587

Gnomad4 FIN exome AF: 0.0929

Gnomad4 NFE exome AF: 0.0280

Gnomad4 OTH exome AF: 0.0465

GnomAD4 genome AF: 0.0632 AC: 9617 AN: 152204 Hom.: 410 Cov.: 33 AF XY: 0.0676 AC XY: 5034 AN XY: 74414

Gnomad4 AFR AF: 0.0885

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0381

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0674

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0230 Hom.: 22

Bravo AF: 0.0671

Asia WGS AF: 0.0870 AC: 303 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.2
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs115171840; hg19: chr9-80851143;