Variant 1-3829920-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014704.4(CEP104):c.1914A>G(p.Arg638=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,614,168 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 363 hom. )

Consequence

CEP104
NM_014704.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-3829920-T-C is Benign according to our data. Variant chr1-3829920-T-C is described in ClinVar as [Benign]. Clinvar id is 475460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP104	NM_014704.4 linkuse as main transcript	c.1914A>G	p.Arg638=	synonymous_variant	14/22	ENST00000378230.8	NP_055519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP104	ENST00000378230.8 linkuse as main transcript	c.1914A>G	p.Arg638=	synonymous_variant	14/22	5	NM_014704.4	ENSP00000367476	P4	O60308-1

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

808

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00897

AC:

2255

AN:

251494

Hom.:

AF XY:

0.00834

AC XY:

1133

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0961

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.000774

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00446

AC:

6513

AN:

1461874

Hom.:

363

Cov.:

AF XY:

0.00431

AC XY:

3135

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.125

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.000302

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00531

AC:

809

AN:

152294

Hom.:

Cov.:

AF XY:

0.00664

AC XY:

494

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000990

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 03, 2019	- -

Joubert syndrome 25

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.3

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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