17-80097289-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_017950.4(CCDC40):c.3066A>G(p.Thr1022=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000577 in 1,613,984 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00061 ( 17 hom. )
Consequence
CCDC40
NM_017950.4 synonymous
NM_017950.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.751
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
?
Variant 17-80097289-A-G is Benign according to our data. Variant chr17-80097289-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 525521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.751 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000295 (45/152348) while in subpopulation SAS AF= 0.00849 (41/4828). AF 95% confidence interval is 0.00643. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.3066A>G | p.Thr1022= | synonymous_variant | 19/20 | ENST00000397545.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.3066A>G | p.Thr1022= | synonymous_variant | 19/20 | 5 | NM_017950.4 | P2 | |
CCDC40 | ENST00000574799.5 | n.2603A>G | non_coding_transcript_exon_variant | 15/16 | 1 | ||||
CCDC40 | ENST00000572253.5 | n.3317A>G | non_coding_transcript_exon_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 152230Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
45
AN:
152230
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00129 AC: 322AN: 249460Hom.: 6 AF XY: 0.00166 AC XY: 225AN XY: 135388
GnomAD3 exomes
AF:
AC:
322
AN:
249460
Hom.:
AF XY:
AC XY:
225
AN XY:
135388
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000606 AC: 886AN: 1461636Hom.: 17 Cov.: 36 AF XY: 0.000868 AC XY: 631AN XY: 727094
GnomAD4 exome
AF:
AC:
886
AN:
1461636
Hom.:
Cov.:
36
AF XY:
AC XY:
631
AN XY:
727094
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000295 AC: 45AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000362 AC XY: 27AN XY: 74508
GnomAD4 genome
?
AF:
AC:
45
AN:
152348
Hom.:
Cov.:
33
AF XY:
AC XY:
27
AN XY:
74508
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2023 | This alteration is classified as likely 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2023 | - - |
CCDC40-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 15, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at