rs12729542

Variant names:

• chr1-3815395-C-T
• rs12729542
• NM_014704.4:c.*7G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-3815395-C-T
• chr1-3815395-C-A

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.*7G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,596,024 control chromosomes in the GnomAD database, including 5,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (406 hom., cov: 34)
  • Exomes 𝑓: 0.083 (5506 hom.)
• Consequence: CEP104 NM_014704.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.981
• Publications: 9 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=-0.94).
• BP6: Variant 1-3815395-C-T is Benign according to our data. Variant chr1-3815395-C-T is described in ClinVar as Benign. ClinVar VariationId is 1263430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.089 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.*7G>A		3_prime_UTR	Exon 22 of 22	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.*7G>A		3_prime_UTR	Exon 22 of 22	ENSP00000367476.3	O60308-1
	CEP104	ENST00000675666.1		c.2717G>A	p.Arg906His	missense	Exon 21 of 21	ENSP00000502548.1	A0A6Q8PH69
	CEP104	ENST00000676052.1		c.*7G>A		3_prime_UTR	Exon 22 of 22	ENSP00000502793.1	A0A6Q8PHR0

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9321 AN: 152212 Hom.: 406 Cov.: 34

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.0655

GnomAD2 exomes AF: 0.0651 AC: 15338 AN: 235484 AF XY: 0.0669

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.0400

Gnomad ASJ exome AF: 0.0857

Gnomad EAS exome AF: 0.00191

Gnomad FIN exome AF: 0.0799

Gnomad NFE exome AF: 0.0914

Gnomad OTH exome AF: 0.0762

GnomAD4 exome AF: 0.0835 AC: 120531 AN: 1443694 Hom.: 5506 Cov.: 28 AF XY: 0.0825 AC XY: 59262 AN XY: 718214

African (AFR) AF: 0.0141 AC: 469 AN: 33236

American (AMR) AF: 0.0420 AC: 1837 AN: 43780

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 2282 AN: 25790

East Asian (EAS) AF: 0.00821 AC: 324 AN: 39482

South Asian (SAS) AF: 0.0450 AC: 3802 AN: 84566

European-Finnish (FIN) AF: 0.0780 AC: 3890 AN: 49878

Middle Eastern (MID) AF: 0.0563 AC: 323 AN: 5738

European-Non Finnish (NFE) AF: 0.0936 AC: 103069 AN: 1101392

Other (OTH) AF: 0.0758 AC: 4535 AN: 59832

GnomAD4 genome AF: 0.0612 AC: 9320 AN: 152330 Hom.: 406 Cov.: 34 AF XY: 0.0600 AC XY: 4466 AN XY: 74484

African (AFR) AF: 0.0167 AC: 696 AN: 41588

American (AMR) AF: 0.0566 AC: 867 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 288 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5180

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4834

European-Finnish (FIN) AF: 0.0827 AC: 877 AN: 10608

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6185 AN: 68020

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0624 Hom.: 157

Bravo AF: 0.0594

Asia WGS AF: 0.0220 AC: 76 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	-0.94
CADD	Benign	0.36
DANN	Benign	0.69
PhyloP100		-0.98
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: rs12729542; hg19: chr1-3731959; COSMIC: COSV107487059; COSMIC: COSV107487059;