1-3815090-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014704.4(CEP104):c.*311_*312insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (36172 hom., cov: 0)
  • Exomes 𝑓: 0.59 (33535 hom.)
• Consequence: CEP104 NM_014704.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.808

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 -10 ACMG points.

• BP6: Variant 1-3815090-C-CT is Benign according to our data. Variant chr1-3815090-C-CT is described in ClinVar as [Benign]. Clinvar id is 1181337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP104	NM_014704.4	c.*311_*312insA		3_prime_UTR_variant	22/22	ENST00000378230.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP104	ENST00000378230.8	c.*311_*312insA		3_prime_UTR_variant	22/22	5	NM_014704.4	P4

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102577 AN: 152038 Hom.: 36115 Cov.: 0

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.639

GnomAD4 exome AF: 0.590 AC: 109798 AN: 186100 Hom.: 33535 Cov.: 0 AF XY: 0.595 AC XY: 58198 AN XY: 97824

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.675 AC: 102689 AN: 152154 Hom.: 36172 Cov.: 0 AF XY: 0.678 AC XY: 50405 AN XY: 74388

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.640

Alfa AF: 0.638 Hom.: 3861

Bravo AF: 0.677

Asia WGS AF: 0.673 AC: 2342 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 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs3838969; hg19: chr1-3731654; COSMIC: COSV65517077; COSMIC: COSV65517077;