rs7212525
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017950.4(CCDC40):c.676+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,607,888 control chromosomes in the GnomAD database, including 56,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.34 ( 11318 hom., cov: 32)
Exomes 𝑓: 0.24 ( 45352 hom. )
Consequence
CCDC40
NM_017950.4 intron
NM_017950.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.10
Genes affected
CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 17-80047415-T-C is Benign according to our data. Variant chr17-80047415-T-C is described in ClinVar as [Benign]. Clinvar id is 178707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80047415-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.676+13T>C | intron_variant | ENST00000397545.9 | |||
CCDC40 | NM_001243342.2 | c.676+13T>C | intron_variant | ||||
CCDC40 | NM_001330508.2 | c.676+13T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.676+13T>C | intron_variant | 5 | NM_017950.4 | P2 | |||
ENST00000695611.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.339 AC: 51547AN: 151974Hom.: 11296 Cov.: 32
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GnomAD3 exomes AF: 0.246 AC: 58669AN: 238144Hom.: 8742 AF XY: 0.247 AC XY: 32036AN XY: 129908
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GnomAD4 exome AF: 0.240 AC: 349238AN: 1455796Hom.: 45352 Cov.: 34 AF XY: 0.240 AC XY: 173865AN XY: 723964
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GnomAD4 genome ? AF: 0.339 AC: 51621AN: 152092Hom.: 11318 Cov.: 32 AF XY: 0.336 AC XY: 25026AN XY: 74372
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | 676+13T>C in intron 4 of CCDC40: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence. It has been identified in 40.2% (1665/4138) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs7212525). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Primary ciliary dyskinesia 15 Benign:3
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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