chr1-3836504-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014704.4(CEP104):c.1308A>T(p.Gly436Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,386,786 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 23)

Exomes 𝑓: 0.0057 ( 17 hom. )

Consequence

CEP104
NM_014704.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00400

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Joubert syndrome 25
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP104 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-3836504-T-A is Benign according to our data. Variant chr1-3836504-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00314 (408/130098) while in subpopulation NFE AF = 0.0049 (306/62424). AF 95% confidence interval is 0.00445. There are 2 homozygotes in GnomAd4. There are 189 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP104	NM_014704.4 link	c.1308A>T	p.Gly436Gly	synonymous_variant	Exon 10 of 22	ENST00000378230.8	NP_055519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP104	ENST00000378230.8 link	c.1308A>T	p.Gly436Gly	synonymous_variant	Exon 10 of 22	5	NM_014704.4	ENSP00000367476.3

Frequencies

GnomAD3 genomes

AF:

0.00314

AC:

408

AN:

129970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00383

Gnomad ASJ

AF:

0.00123

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00294

Gnomad FIN

AF:

0.000995

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00490

Gnomad OTH

AF:

0.00353

GnomAD2 exomes

AF:

0.00273

AC:

670

AN:

245616

AF XY:

0.00275

show subpopulations

Gnomad AFR exome

AF:

0.000808

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000558

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00572

AC:

7194

AN:

1256688

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

3526

AN XY:

631190

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

24788

American (AMR)

AF:

0.00291

AC:

124

AN:

42660

Ashkenazi Jewish (ASJ)

AF:

0.00152

AC:

AN:

22344

East Asian (EAS)

AF:

0.0000289

AC:

AN:

34562

South Asian (SAS)

AF:

0.00213

AC:

172

AN:

80936

European-Finnish (FIN)

AF:

0.000856

AC:

AN:

45570

Middle Eastern (MID)

AF:

0.00307

AC:

AN:

4556

European-Non Finnish (NFE)

AF:

0.00684

AC:

6501

AN:

950502

Other (OTH)

AF:

0.00546

AC:

277

AN:

50770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

340

680

1020

1360

1700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00314

AC:

408

AN:

130098

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

189

AN XY:

61830

show subpopulations

African (AFR)

AF:

0.000848

AC:

AN:

35376

American (AMR)

AF:

0.00382

AC:

AN:

11516

Ashkenazi Jewish (ASJ)

AF:

0.00123

AC:

AN:

3244

East Asian (EAS)

AF:

0.00

AC:

AN:

3926

South Asian (SAS)

AF:

0.00293

AC:

AN:

3756

European-Finnish (FIN)

AF:

0.000995

AC:

AN:

7034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00490

AC:

306

AN:

62424

Other (OTH)

AF:

0.00348

AC:

AN:

1724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00355

Hom.:

EpiCase

AF:

0.00475

EpiControl

AF:

0.00369

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEP104: BP4, BP7, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Joubert syndrome 25

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.58

CADD

Benign

1.0

(source)

DANN

Benign

0.67

PhyloP100

-0.0040

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over