rs6663840

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014704.4(CEP104):c.2152-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,611,218 control chromosomes in the GnomAD database, including 95,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12838 hom., cov: 33)

Exomes 𝑓: 0.33 ( 82566 hom. )

Consequence

CEP104
NM_014704.4 intron

Scores

Splicing: ADA: 0.00001617

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.184

Publications

25 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-3826755-G-A is Benign according to our data. Variant chr1-3826755-G-A is described in ClinVar as Benign. ClinVar VariationId is 1209725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP104	NM_014704.4 link	c.2152-11C>T		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.2152-11C>T		intron_variant	Intron 15 of 21	5	NM_014704.4	ENSP00000367476.3		O60308-1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59498

AN:

151900

Hom.:

12816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.508

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.381

AC:

95695

AN:

251236

AF XY:

0.380

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.557

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.327

AC:

477340

AN:

1459200

Hom.:

82566

Cov.:

AF XY:

0.331

AC XY:

240563

AN XY:

726030

show subpopulations

African (AFR)

AF:

0.564

AC:

18853

AN:

33418

American (AMR)

AF:

0.381

AC:

17044

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

10101

AN:

26108

East Asian (EAS)

AF:

0.503

AC:

19961

AN:

39692

South Asian (SAS)

AF:

0.506

AC:

43615

AN:

86188

European-Finnish (FIN)

AF:

0.312

AC:

16649

AN:

53406

Middle Eastern (MID)

AF:

0.415

AC:

2391

AN:

5764

European-Non Finnish (NFE)

AF:

0.295

AC:

327388

AN:

1109620

Other (OTH)

AF:

0.354

AC:

21338

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

15000

30001

45001

60002

75002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11160

22320

33480

44640

55800

<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:

0.392

AC:

59574

AN:

152018

Hom.:

12838

Cov.:

AF XY:

0.394

AC XY:

29291

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.556

AC:

23041

AN:

41428

American (AMR)

AF:

0.340

AC:

5189

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1267

AN:

3468

East Asian (EAS)

AF:

0.556

AC:

2879

AN:

5178

South Asian (SAS)

AF:

0.508

AC:

2450

AN:

4824

European-Finnish (FIN)

AF:

0.322

AC:

3397

AN:

10566

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20243

AN:

67960

Other (OTH)

AF:

0.373

AC:

788

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1795

3590

5386

7181

8976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.336

Hom.:

31151

Bravo

AF:

0.402

Asia WGS

AF:

0.528

AC:

1837

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 25

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 13, 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

-0.87

CADD

Benign

(source)

DANN

Benign

0.37

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.19

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