1-3815401-G-A

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.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,603,542 control chromosomes in the GnomAD database, including 13,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1339 hom., cov: 34)
  • Exomes 𝑓: 0.13 (12184 hom.)
• Consequence: CEP104 NM_014704.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

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=-0.74).
• BP6: Variant 1-3815401-G-A is Benign according to our data. Variant chr1-3815401-G-A is described in ClinVar as [Benign]. Clinvar id is 1241222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP104	NM_014704.4	c.*1C>T		3_prime_UTR_variant	22/22	ENST00000378230.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP104	ENST00000378230.8	c.*1C>T		3_prime_UTR_variant	22/22	5	NM_014704.4	P4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19612 AN: 152186 Hom.: 1340 Cov.: 34

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.117 AC: 28454 AN: 242360 Hom.: 1834 AF XY: 0.118 AC XY: 15495 AN XY: 131256

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0640

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0427

Gnomad SAS exome AF: 0.0987

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.127 AC: 183806 AN: 1451238 Hom.: 12184 Cov.: 30 AF XY: 0.126 AC XY: 91161 AN XY: 721976

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0677

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0479

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.129 AC: 19633 AN: 152304 Hom.: 1339 Cov.: 34 AF XY: 0.128 AC XY: 9525 AN XY: 74486

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0473

Gnomad4 SAS AF: 0.0940

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.127

Alfa AF: 0.111 Hom.: 389

Bravo AF: 0.127

Asia WGS AF: 0.0720 AC: 255 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.5
Dann	Benign	0.83

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: rs12728401; hg19: chr1-3731965;