Variant 1-3815539-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014704.4(CEP104):c.2663-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,535,868 control chromosomes in the GnomAD database, including 258,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.65 ( 33269 hom., cov: 33)

Exomes 𝑓: 0.57 ( 224767 hom. )

Consequence

CEP104
NM_014704.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.59

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

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-3815539-T-C is Benign according to our data. Variant chr1-3815539-T-C is described in ClinVar as [Benign]. Clinvar id is 1209723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP104	NM_014704.4 linkuse as main transcript	c.2663-22A>G		intron_variant		ENST00000378230.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP104	ENST00000378230.8 linkuse as main transcript	c.2663-22A>G		intron_variant		5	NM_014704.4	P4	O60308-1

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

98249

AN:

152026

Hom.:

33213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.679

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.606

GnomAD3 exomes

AF:

0.593

AC:

113897

AN:

192116

Hom.:

34203

AF XY:

0.593

AC XY:

61243

AN XY:

103334

show subpopulations

Gnomad AFR exome

AF:

0.868

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.560

Gnomad SAS exome

AF:

0.676

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.578

GnomAD4 exome

AF:

0.566

AC:

783452

AN:

1383724

Hom.:

224767

Cov.:

AF XY:

0.569

AC XY:

388599

AN XY:

683074

show subpopulations

Gnomad4 AFR exome

AF:

0.874

Gnomad4 AMR exome

AF:

0.503

Gnomad4 ASJ exome

AF:

0.660

Gnomad4 EAS exome

AF:

0.503

Gnomad4 SAS exome

AF:

0.676

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.594

GnomAD4 genome

AF:

0.647

AC:

98363

AN:

152144

Hom.:

33269

Cov.:

AF XY:

0.647

AC XY:

48124

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.863

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.660

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.607

Alfa

AF:

0.544

Hom.:

3186

Bravo

AF:

0.648

Asia WGS

AF:

0.627

AC:

2182

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 25

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.035

DANN

Benign

0.38

BranchPoint Hunter

1.0

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

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