rs6688969

Variant names:

• chr1-3826827-C-T
• rs6688969
• NM_014704.4:c.2152-83G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-3826827-C-T
• chr1-3826827-C-A
• chr1-3826827-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014704.4(CEP104):​c.2152-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,394,684 control chromosomes in the GnomAD database, including 77,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7251 hom., cov: 33)
  • Exomes 𝑓: 0.33 (70200 hom.)
• Consequence: CEP104 NM_014704.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.670
• Publications: 8 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):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 25

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-3826827-C-T is Benign according to our data. Variant chr1-3826827-C-T is described in ClinVar as Benign. ClinVar VariationId is 1242626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014704.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP104	NM_014704.4	MANE Select	c.2152-83G>A		intron	N/A	NP_055519.1	O60308-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP104	ENST00000378230.8	TSL:5 MANE Select	c.2152-83G>A		intron	N/A	ENSP00000367476.3	O60308-1
	CEP104	ENST00000675666.1		c.2152-83G>A		intron	N/A	ENSP00000502548.1	A0A6Q8PH69
	CEP104	ENST00000676052.1		c.2170-83G>A		intron	N/A	ENSP00000502793.1	A0A6Q8PHR0

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44620 AN: 151584 Hom.: 7244 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.332 AC: 412118 AN: 1242982 Hom.: 70200 AF XY: 0.336 AC XY: 210865 AN XY: 627878

African (AFR) AF: 0.173 AC: 4845 AN: 28042

American (AMR) AF: 0.343 AC: 14439 AN: 42098

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 7777 AN: 24340

East Asian (EAS) AF: 0.449 AC: 17248 AN: 38390

South Asian (SAS) AF: 0.446 AC: 35697 AN: 80010

European-Finnish (FIN) AF: 0.410 AC: 21726 AN: 52974

Middle Eastern (MID) AF: 0.324 AC: 1718 AN: 5306

European-Non Finnish (NFE) AF: 0.317 AC: 290891 AN: 919066

Other (OTH) AF: 0.337 AC: 17777 AN: 52756

GnomAD4 genome AF: 0.294 AC: 44644 AN: 151702 Hom.: 7251 Cov.: 33 AF XY: 0.303 AC XY: 22419 AN XY: 74102

African (AFR) AF: 0.172 AC: 7074 AN: 41184

American (AMR) AF: 0.291 AC: 4440 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2624 AN: 5172

South Asian (SAS) AF: 0.468 AC: 2247 AN: 4806

European-Finnish (FIN) AF: 0.433 AC: 4569 AN: 10546

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21562 AN: 67968

Other (OTH) AF: 0.296 AC: 622 AN: 2104

Alfa AF: 0.290 Hom.: 9993

Bravo AF: 0.279

Asia WGS AF: 0.462 AC: 1602 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.71
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6688969; hg19: chr1-3743391; COSMIC: COSV65517518; COSMIC: COSV65517518;