Genetic Variant CEP104:c.*311_*312insA (chr1-3815090-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_014704.4(CEP104):c.*311_*312insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.67 ( 36172 hom., cov: 0)

Exomes 𝑓: 0.59 ( 33535 hom. )

Consequence

CEP104
NM_014704.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.808

Publications

3 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 -10 ACMG points.

BP6

Variant 1-3815090-C-CT is Benign according to our data. Variant chr1-3815090-C-CT is described in ClinVar as [Benign]. Clinvar id is 1181337.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP104	NM_014704.4 link	c.311_312insA		3_prime_UTR_variant	Exon 22 of 22	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.311_312insA		3_prime_UTR_variant	Exon 22 of 22	5	NM_014704.4	ENSP00000367476.3		O60308-1

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

102577

AN:

152038

Hom.:

36115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.695

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.639

GnomAD4 exome

AF:

0.590

AC:

109798

AN:

186100

Hom.:

33535

Cov.:

AF XY:

0.595

AC XY:

58198

AN XY:

97824

show subpopulations

African (AFR)

AF:

0.881

AC:

4091

AN:

4642

American (AMR)

AF:

0.561

AC:

3727

AN:

6644

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

3972

AN:

6056

East Asian (EAS)

AF:

0.591

AC:

5942

AN:

10058

South Asian (SAS)

AF:

0.681

AC:

14361

AN:

21090

European-Finnish (FIN)

AF:

0.643

AC:

7218

AN:

11226

Middle Eastern (MID)

AF:

0.643

AC:

558

AN:

868

European-Non Finnish (NFE)

AF:

0.552

AC:

63063

AN:

114292

Other (OTH)

AF:

0.612

AC:

6866

AN:

11224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2039

4078

6117

8156

10195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.675

AC:

102689

AN:

152154

Hom.:

36172

Cov.:

AF XY:

0.678

AC XY:

50405

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.892

AC:

37039

AN:

41544

American (AMR)

AF:

0.555

AC:

8481

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

2306

AN:

3468

East Asian (EAS)

AF:

0.660

AC:

3417

AN:

5176

South Asian (SAS)

AF:

0.695

AC:

3356

AN:

4826

European-Finnish (FIN)

AF:

0.686

AC:

7257

AN:

10572

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38791

AN:

67958

Other (OTH)

AF:

0.640

AC:

1352

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1634

3268

4903

6537

8171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.638

Hom.:

3861

Bravo

AF:

0.677

Asia WGS

AF:

0.673

AC:

2342

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 06, 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

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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1-3815090-C-CT

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