1-3815631-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.2663-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 671,460 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (45 hom., cov: 33)
  • Exomes 𝑓: 0.011 (274 hom.)
• Consequence: CEP104 NM_014704.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.274

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 1-3815631-C-T is Benign according to our data. Variant chr1-3815631-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP104	NM_014704.4	c.2663-114G>A		intron_variant		ENST00000378230.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP104	ENST00000378230.8	c.2663-114G>A		intron_variant		5	NM_014704.4	P4

Frequencies

GnomAD3 genomes AF: 0.00902 AC: 1372 AN: 152140 Hom.: 46 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0115 AC: 5960 AN: 519206 Hom.: 274 AF XY: 0.0114 AC XY: 3059 AN XY: 269206

Gnomad4 AFR exome AF: 0.00135

Gnomad4 AMR exome AF: 0.0429

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.0121

Gnomad4 FIN exome AF: 0.0227

Gnomad4 NFE exome AF: 0.000581

Gnomad4 OTH exome AF: 0.00913

GnomAD4 genome AF: 0.00900 AC: 1371 AN: 152254 Hom.: 45 Cov.: 33 AF XY: 0.0104 AC XY: 771 AN XY: 74436

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00635 Hom.: 3

Bravo AF: 0.0109

Asia WGS AF: 0.0410 AC: 141 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.7
Dann	Benign	0.48

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: rs117132607; hg19: chr1-3732195;