rs56502737
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_017950.4(CCDC40):c.2868G>A(p.Lys956=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0305 in 1,614,018 control chromosomes in the GnomAD database, including 1,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.032 ( 114 hom., cov: 34)
Exomes 𝑓: 0.030 ( 1036 hom. )
Consequence
CCDC40
NM_017950.4 synonymous
NM_017950.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.88
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 17-80095298-G-A is Benign according to our data. Variant chr17-80095298-G-A is described in ClinVar as [Benign]. Clinvar id is 226492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80095298-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.2868G>A | p.Lys956= | synonymous_variant | 18/20 | ENST00000397545.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.2868G>A | p.Lys956= | synonymous_variant | 18/20 | 5 | NM_017950.4 | P2 | |
CCDC40 | ENST00000574799.5 | n.2405G>A | non_coding_transcript_exon_variant | 14/16 | 1 | ||||
CCDC40 | ENST00000572253.5 | n.3119G>A | non_coding_transcript_exon_variant | 5/6 | 2 | ||||
CCDC40 | ENST00000575431.1 | n.512G>A | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0323 AC: 4911AN: 152268Hom.: 115 Cov.: 34
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GnomAD3 exomes AF: 0.0379 AC: 9432AN: 249086Hom.: 263 AF XY: 0.0391 AC XY: 5285AN XY: 135308
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GnomAD4 exome AF: 0.0304 AC: 44395AN: 1461632Hom.: 1036 Cov.: 32 AF XY: 0.0312 AC XY: 22699AN XY: 727110
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GnomAD4 genome ? AF: 0.0322 AC: 4908AN: 152386Hom.: 114 Cov.: 34 AF XY: 0.0339 AC XY: 2528AN XY: 74524
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 02, 2015 | p.Lys956Lys in exon 18 of CCDC40: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 3.7% (4610/11952 4) of all ethnicity chromosomes by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org; dbSNP rs1982243). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Primary ciliary dyskinesia 15 Benign:1
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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at