7-130393983-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_018718.3(CEP41):c.*4908G>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 0.000883 in 454,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00093 ( 0 hom. )
Consequence
CEP41
NM_018718.3 3_prime_UTR
NM_018718.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.236
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000795 (121/152284) while in subpopulation NFE AF= 0.00141 (96/68024). AF 95% confidence interval is 0.00118. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| CEP41 | NM_018718.3 | c.*4908G>A | 3_prime_UTR_variant | 11/11 | ENST00000223208.10 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CEP41 | ENST00000223208.10 | c.*4908G>A | 3_prime_UTR_variant | 11/11 | 1 | NM_018718.3 | P3 | ||
| CEP41 | ENST00000541543.6 | c.*4908G>A | 3_prime_UTR_variant | 11/11 | 2 | ||||
| CEP41 | ENST00000675649.1 | c.*4908G>A | 3_prime_UTR_variant | 9/9 |
Frequencies
GnomAD3 genomes 0.000795 AC: 121AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000703 AC: 90AN: 128036Hom.: 0 AF XY: 0.000628 AC XY: 44AN XY: 70116
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GnomAD4 exome AF: 0.000928 AC: 280AN: 301794Hom.: 0 Cov.: 0 AF XY: 0.000878 AC XY: 151AN XY: 171996
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GnomAD4 genome 0.000795 AC: 121AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52AN XY: 74464
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 15 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at