1-3815093-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014704.4(CEP104):c.*309G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 344,524 control chromosomes in the GnomAD database, including 3,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2196 hom., cov: 34)
  • Exomes 𝑓: 0.11 (1478 hom.)
• Consequence: CEP104 NM_014704.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.195

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-3815093-C-T is Benign according to our data. Variant chr1-3815093-C-T is described in ClinVar as [Benign]. Clinvar id is 1231645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP104	NM_014704.4	c.*309G>A		3_prime_UTR_variant	22/22	ENST00000378230.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP104	ENST00000378230.8	c.*309G>A		3_prime_UTR_variant	22/22	5	NM_014704.4	P4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24198 AN: 151822 Hom.: 2195 Cov.: 34

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.114 AC: 21963 AN: 192584 Hom.: 1478 Cov.: 0 AF XY: 0.113 AC XY: 11413 AN XY: 101384

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.0845

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.0506

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.159 AC: 24229 AN: 151940 Hom.: 2196 Cov.: 34 AF XY: 0.157 AC XY: 11697 AN XY: 74268

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0477

Gnomad4 SAS AF: 0.0949

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.146

Alfa AF: 0.147 Hom.: 402

Bravo AF: 0.161

Asia WGS AF: 0.0780 AC: 275 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs34060840; hg19: chr1-3731657;