rs753690300
Variant names:
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_017950.4(CCDC40):c.1038G>A(p.Glu346Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,270 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 Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CCDC40
NM_017950.4 synonymous
NM_017950.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.57
Publications
1 publications found
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]
CCDC40 Gene-Disease associations (from GenCC):
- primary ciliary dyskinesia 15Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autoimmune diseaseInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 17-80050162-G-A is Benign according to our data. Variant chr17-80050162-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 260947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.57 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_017950.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CCDC40 | NM_017950.4 | MANE Select | c.1038G>A | p.Glu346Glu | synonymous | Exon 7 of 20 | NP_060420.2 | ||
| CCDC40 | NM_001243342.2 | c.1038G>A | p.Glu346Glu | synonymous | Exon 7 of 18 | NP_001230271.1 | |||
| CCDC40 | NM_001330508.2 | c.1038G>A | p.Glu346Glu | synonymous | Exon 7 of 11 | NP_001317437.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CCDC40 | ENST00000397545.9 | TSL:5 MANE Select | c.1038G>A | p.Glu346Glu | synonymous | Exon 7 of 20 | ENSP00000380679.4 | ||
| CCDC40 | ENST00000374876.4 | TSL:1 | c.1038G>A | p.Glu346Glu | synonymous | Exon 7 of 9 | ENSP00000364010.4 | ||
| CCDC40 | ENST00000574799.5 | TSL:1 | n.575G>A | non_coding_transcript_exon | Exon 3 of 16 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000403 AC: 1AN: 247862 AF XY: 0.00000741 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
247862
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461270Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726942 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461270
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
726942
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
52970
Middle Eastern (MID)
AF:
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111966
Other (OTH)
AF:
AC:
0
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
-
-
1
Primary ciliary dyskinesia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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