Genetic Variant CEP104:c.2152-42C>G (chr1-3826786-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014704.4(CEP104):c.2152-42C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 1,559,322 control chromosomes in the GnomAD database, including 1,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 107 hom., cov: 34)

Exomes 𝑓: 0.029 ( 1103 hom. )

Consequence

CEP104
NM_014704.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.120

Variant links:

Genes affected

CEP104 (HGNC:24866): (centrosomal protein 104) This gene encodes a centrosomal protein required for ciliogenesis and for ciliary tip structural integrity. The mammalian protein contains three amino-terminal hydrophobic domains, two glycosylation sites, four cysteine-rich motifs, and two regions with homology to the glutamate receptor ionotropic, NMDA 1 protein. During ciliogenesis, the encoded protein translocates from the distal tips of the centrioles to the tip of the elongating cilium. Knockdown of the protein in human retinal pigment cells results in severe defects in ciliogenesis with structural deformities at the ciliary tips. Allelic variants of this gene are associated with the autosomal-recessive disorder Joubert syndrome, which is characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. [provided by RefSeq, Feb 2016]

CEP104 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-3826786-G-C is Benign according to our data. Variant chr1-3826786-G-C is described in ClinVar as [Benign]. Clinvar id is 1288966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP104	NM_014704.4 link	c.2152-42C>G		intron_variant	Intron 15 of 21	ENST00000378230.8	NP_055519.1	O60308-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP104	ENST00000378230.8 link	c.2152-42C>G		intron_variant	Intron 15 of 21	5	NM_014704.4	ENSP00000367476.3		O60308-1

Frequencies

GnomAD3 genomes

AF:

0.0253

AC:

3852

AN:

152194

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0426

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.0841

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0459

AC:

11471

AN:

250152

Hom.:

448

AF XY:

0.0461

AC XY:

6229

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.0887

Gnomad ASJ exome

AF:

0.0543

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.0861

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.0188

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0286

AC:

40278

AN:

1407010

Hom.:

1103

Cov.:

AF XY:

0.0300

AC XY:

21082

AN XY:

703564

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.0820

Gnomad4 ASJ exome

AF:

0.0525

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.0846

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0253

AC:

3851

AN:

152312

Hom.:

107

Cov.:

AF XY:

0.0269

AC XY:

2001

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.0425

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.105

Gnomad4 SAS

AF:

0.0839

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0271

Hom.:

Bravo

AF:

0.0268

Asia WGS

AF:

0.0790

AC:

273

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 21, 2018

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

-0.91

CADD

Benign

1.7

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over