rs1929402

Variant names:

• chr9-78248172-G-A
• rs1929402
• NM_001330691.3:c.893-119G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CEP78	NM_001330691.3	c.893-119G>A		intron_variant	Intron 6 of 16	ENST00000643273.2	NP_001317620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP78	ENST00000643273.2	c.893-119G>A		intron_variant	Intron 6 of 16		NM_001330691.3	ENSP00000496423.2

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

African (AFR) AF: 0.829 AC: 10912 AN: 13162

American (AMR) AF: 0.865 AC: 20600 AN: 23822

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 14278 AN: 18202

East Asian (EAS) AF: 0.581 AC: 18000 AN: 30984

South Asian (SAS) AF: 0.729 AC: 40231 AN: 55170

European-Finnish (FIN) AF: 0.802 AC: 36999 AN: 46120

Middle Eastern (MID) AF: 0.776 AC: 1748 AN: 2254

European-Non Finnish (NFE) AF: 0.786 AC: 241760 AN: 307412

Other (OTH) AF: 0.780 AC: 22277 AN: 28548

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

African (AFR) AF: 0.835 AC: 34675 AN: 41526

American (AMR) AF: 0.841 AC: 12857 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2732 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3339 AN: 5170

South Asian (SAS) AF: 0.716 AC: 3456 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8593 AN: 10594

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53506 AN: 68010

Other (OTH) AF: 0.784 AC: 1658 AN: 2116

Alfa AF: 0.788 Hom.: 158658

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.23
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1929402; hg19: chr9-80863088;