chr17-80089904-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017950.4(CCDC40):c.2832+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,613,574 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0048 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 4 hom. )
Consequence
CCDC40
NM_017950.4 intron
NM_017950.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.517
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 17-80089904-G-A is Benign according to our data. Variant chr17-80089904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00476 (725/152386) while in subpopulation AFR AF= 0.0167 (693/41598). AF 95% confidence interval is 0.0156. There are 8 homozygotes in gnomad4. There are 345 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.2832+20G>A | intron_variant | ENST00000397545.9 | NP_060420.2 | |||
CCDC40 | NM_001243342.2 | c.2832+20G>A | intron_variant | NP_001230271.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.2832+20G>A | intron_variant | 5 | NM_017950.4 | ENSP00000380679.4 |
Frequencies
GnomAD3 genomes AF: 0.00478 AC: 728AN: 152268Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00123 AC: 304AN: 248050Hom.: 4 AF XY: 0.000861 AC XY: 116AN XY: 134774
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GnomAD4 exome AF: 0.000552 AC: 807AN: 1461188Hom.: 4 Cov.: 32 AF XY: 0.000483 AC XY: 351AN XY: 726896
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GnomAD4 genome AF: 0.00476 AC: 725AN: 152386Hom.: 8 Cov.: 32 AF XY: 0.00463 AC XY: 345AN XY: 74522
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 05, 2020 | See Variant Classification Assertion Criteria. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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