1-3815395-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.*7G>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 0.0814 in 1,596,024 control chromosomes in the GnomAD database, including 5,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (406 hom., cov: 34)
  • Exomes 𝑓: 0.083 (5506 hom.)
• Consequence: CEP104 NM_014704.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.981

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=-0.94).
• BP6: Variant 1-3815395-C-T is Benign according to our data. Variant chr1-3815395-C-T is described in ClinVar as [Benign]. Clinvar id is 1263430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP104	NM_014704.4	c.*7G>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.*7G>A		3_prime_UTR_variant	22/22	5	NM_014704.4	P4

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9321 AN: 152212 Hom.: 406 Cov.: 34

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0655

GnomAD3 exomes AF: 0.0651 AC: 15338 AN: 235484 Hom.: 600 AF XY: 0.0669 AC XY: 8535 AN XY: 127576

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.0400

Gnomad ASJ exome AF: 0.0857

Gnomad EAS exome AF: 0.00191

Gnomad SAS exome AF: 0.0432

Gnomad FIN exome AF: 0.0799

Gnomad NFE exome AF: 0.0914

Gnomad OTH exome AF: 0.0762

GnomAD4 exome AF: 0.0835 AC: 120531 AN: 1443694 Hom.: 5506 Cov.: 28 AF XY: 0.0825 AC XY: 59262 AN XY: 718214

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0420

Gnomad4 ASJ exome AF: 0.0885

Gnomad4 EAS exome AF: 0.00821

Gnomad4 SAS exome AF: 0.0450

Gnomad4 FIN exome AF: 0.0780

Gnomad4 NFE exome AF: 0.0936

Gnomad4 OTH exome AF: 0.0758

GnomAD4 genome AF: 0.0612 AC: 9320 AN: 152330 Hom.: 406 Cov.: 34 AF XY: 0.0600 AC XY: 4466 AN XY: 74484

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0829

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.0909

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0624 Hom.: 157

Bravo AF: 0.0594

Asia WGS AF: 0.0220 AC: 76 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

Aug 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.36
Dann	Benign	0.69

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: rs12729542; hg19: chr1-3731959;