rs1057650

Variant names:

• chr9-78264233-C-T
• rs1057650
• NM_001330691.3:c.1542C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.545

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 -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 rank	MANE	Protein	UniProt
CEP78	NM_001330691.3	c.1542C>T	p.Ile514Ile	synonymous_variant	Exon 13 of 17	ENST00000643273.2	NP_001317620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2	c.1542C>T	p.Ile514Ile	synonymous_variant	Exon 13 of 17		NM_001330691.3	ENSP00000496423.2

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14273 AN: 151952 Hom.: 764 Cov.: 32

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

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.: 30 AF XY: 0.0833 AC XY: 60425 AN XY: 725350

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.: 32 AF XY: 0.0911 AC XY: 6771 AN XY: 74330

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

Submissions by phenotype

not provided Benign:3

-

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

- -

May 04, 2021

GeneDx

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
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

Other links and lift over

dbSNP: rs1057650; hg19: chr9-80879149; COSMIC: COSV52846107; COSMIC: COSV52846107;