rs3838969

Variant names:

• chr1-3815090-C-CT
• rs3838969
• NM_014704.4:c.*311_*312insA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CEP104 Gene-Disease associations (from GenCC):

• Joubert syndrome 25

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CEP104	NM_014704.4	c.*311_*312insA		3_prime_UTR_variant	Exon 22 of 22	ENST00000378230.8	NP_055519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP104	ENST00000378230.8	c.*311_*312insA		3_prime_UTR_variant	Exon 22 of 22	5	NM_014704.4	ENSP00000367476.3

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

African (AFR) AF: 0.881 AC: 4091 AN: 4642

American (AMR) AF: 0.561 AC: 3727 AN: 6644

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 3972 AN: 6056

East Asian (EAS) AF: 0.591 AC: 5942 AN: 10058

South Asian (SAS) AF: 0.681 AC: 14361 AN: 21090

European-Finnish (FIN) AF: 0.643 AC: 7218 AN: 11226

Middle Eastern (MID) AF: 0.643 AC: 558 AN: 868

European-Non Finnish (NFE) AF: 0.552 AC: 63063 AN: 114292

Other (OTH) AF: 0.612 AC: 6866 AN: 11224

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

African (AFR) AF: 0.892 AC: 37039 AN: 41544

American (AMR) AF: 0.555 AC: 8481 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3417 AN: 5176

South Asian (SAS) AF: 0.695 AC: 3356 AN: 4826

European-Finnish (FIN) AF: 0.686 AC: 7257 AN: 10572

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38791 AN: 67958

Other (OTH) AF: 0.640 AC: 1352 AN: 2114

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

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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