17-80081797-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017950.4(CCDC40):​c.1806+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CCDC40
NM_017950.4 splice_region, intron

Scores

2
Splicing: ADA: 0.001318
2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.829

Publications

0 publications found
Variant links:
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 15
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
  • primary ciliary dyskinesia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autoimmune disease
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 17-80081797-C-T is Benign according to our data. Variant chr17-80081797-C-T is described in ClinVar as [Benign]. Clinvar id is 414636.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC40NM_017950.4 linkc.1806+8C>T splice_region_variant, intron_variant Intron 11 of 19 ENST00000397545.9 NP_060420.2 Q4G0X9-1
CCDC40NM_001243342.2 linkc.1806+8C>T splice_region_variant, intron_variant Intron 11 of 17 NP_001230271.1 Q4G0X9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC40ENST00000397545.9 linkc.1806+8C>T splice_region_variant, intron_variant Intron 11 of 19 5 NM_017950.4 ENSP00000380679.4 Q4G0X9-1
CCDC40ENST00000574799.5 linkn.1343+8C>T splice_region_variant, intron_variant Intron 7 of 15 1
CCDC40ENST00000572253.5 linkn.355C>T non_coding_transcript_exon_variant Exon 1 of 6 2
CCDC40ENST00000374877.7 linkc.1806+8C>T splice_region_variant, intron_variant Intron 11 of 17 5 ENSP00000364011.3 Q4G0X9-2

Frequencies

GnomAD3 genomes
AF:
0.000677
AC:
103
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00220
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000958
GnomAD2 exomes
AF:
0.000202
AC:
50
AN:
247810
AF XY:
0.000193
show subpopulations
Gnomad AFR exome
AF:
0.00268
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000625
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.000164
AC:
239
AN:
1461584
Hom.:
0
Cov.:
31
AF XY:
0.000165
AC XY:
120
AN XY:
727100
show subpopulations
African (AFR)
AF:
0.00287
AC:
96
AN:
33474
American (AMR)
AF:
0.0000447
AC:
2
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.0000504
AC:
2
AN:
39694
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53258
Middle Eastern (MID)
AF:
0.000175
AC:
1
AN:
5710
European-Non Finnish (NFE)
AF:
0.000112
AC:
125
AN:
1111988
Other (OTH)
AF:
0.000199
AC:
12
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
17
34
50
67
84
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000676
AC:
103
AN:
152306
Hom.:
0
Cov.:
33
AF XY:
0.000631
AC XY:
47
AN XY:
74464
show subpopulations
African (AFR)
AF:
0.00219
AC:
91
AN:
41574
American (AMR)
AF:
0.000392
AC:
6
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000588
AC:
4
AN:
68022
Other (OTH)
AF:
0.000948
AC:
2
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
5
10
16
21
26
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000605
Hom.:
0
Bravo
AF:
0.000952
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Jan 19, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

CCDC40-related disorder Benign:1
May 08, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.2
DANN
Benign
0.80
PhyloP100
-0.83

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0013
dbscSNV1_RF
Benign
0.022
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs182104049; hg19: chr17-78055596; API