rs1929402

Positions:

• chr9-78248172-G-A

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.893-119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 677,880 control chromosomes in the GnomAD database, including 207,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48849 hom., cov: 32)
  • Exomes 𝑓: 0.77 (158649 hom.)
• Consequence: CEP78 NM_001330691.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.781

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=-0.88).
• BP6: Variant 9-78248172-G-A is Benign according to our data. Variant chr9-78248172-G-A is described in ClinVar as [Benign]. Clinvar id is 1260072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP78	NM_001330691.3	c.893-119G>A		intron_variant		ENST00000643273.2	NP_001317620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2	c.893-119G>A		intron_variant			NM_001330691.3	ENSP00000496423	P4

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121598 AN: 152088 Hom.: 48811 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.774 AC: 406805 AN: 525674 Hom.: 158649 AF XY: 0.771 AC XY: 219529 AN XY: 284730

Gnomad4 AFR exome AF: 0.829

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.581

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.780

GnomAD4 genome AF: 0.800 AC: 121690 AN: 152206 Hom.: 48849 Cov.: 32 AF XY: 0.799 AC XY: 59484 AN XY: 74426

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.784

Alfa AF: 0.784 Hom.: 101683

Bravo AF: 0.806

Asia WGS AF: 0.644 AC: 2242 AN: 3476

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 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.23

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: rs1929402; hg19: chr9-80863088;