GeneBe

chr7-130401961-G-GA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018718.3(CEP41):​c.575-14dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,616 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CEP41
NM_018718.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

0 publications found
Variant links:
Genes affected
CEP41 (HGNC:12370): (centrosomal protein 41) This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
CEP41 Gene-Disease associations (from GenCC):
  • Joubert syndrome 15
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • Joubert syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Joubert syndrome with ocular defect
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEP41NM_018718.3 linkc.575-14dupT intron_variant Intron 7 of 10 ENST00000223208.10 NP_061188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEP41ENST00000223208.10 linkc.575-14_575-13insT intron_variant Intron 7 of 10 1 NM_018718.3 ENSP00000223208.4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.93e-7
AC:
1
AN:
1442616
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
718678
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33062
American (AMR)
AF:
0.00
AC:
0
AN:
44670
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26000
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39572
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85872
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53322
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
9.14e-7
AC:
1
AN:
1094688
Other (OTH)
AF:
0.00
AC:
0
AN:
59690
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.2

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

Other links and lift over

dbSNP: rs144531086; hg19: chr7-130041802; API