17-80099790-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017950.4(CCDC40):​c.*15T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,610,396 control chromosomes in the GnomAD database, including 73,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10337 hom., cov: 32)
Exomes 𝑓: 0.29 ( 63205 hom. )

Consequence

CCDC40
NM_017950.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.649
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 17-80099790-T-C is Benign according to our data. Variant chr17-80099790-T-C is described in ClinVar as [Benign]. Clinvar id is 162853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80099790-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC40NM_017950.4 linkuse as main transcriptc.*15T>C 3_prime_UTR_variant 20/20 ENST00000397545.9 NP_060420.2 Q4G0X9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC40ENST00000397545.9 linkuse as main transcriptc.*15T>C 3_prime_UTR_variant 20/205 NM_017950.4 ENSP00000380679.4 Q4G0X9-1
CCDC40ENST00000574799.5 linkuse as main transcriptn.2981T>C non_coding_transcript_exon_variant 16/161

Frequencies

GnomAD3 genomes
AF:
0.352
AC:
53366
AN:
151808
Hom.:
10320
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.517
Gnomad AMI
AF:
0.337
Gnomad AMR
AF:
0.216
Gnomad ASJ
AF:
0.257
Gnomad EAS
AF:
0.424
Gnomad SAS
AF:
0.326
Gnomad FIN
AF:
0.333
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.287
Gnomad OTH
AF:
0.328
GnomAD3 exomes
AF:
0.302
AC:
73977
AN:
245030
Hom.:
11950
AF XY:
0.305
AC XY:
40779
AN XY:
133664
show subpopulations
Gnomad AFR exome
AF:
0.521
Gnomad AMR exome
AF:
0.159
Gnomad ASJ exome
AF:
0.266
Gnomad EAS exome
AF:
0.409
Gnomad SAS exome
AF:
0.333
Gnomad FIN exome
AF:
0.329
Gnomad NFE exome
AF:
0.289
Gnomad OTH exome
AF:
0.309
GnomAD4 exome
AF:
0.288
AC:
420697
AN:
1458470
Hom.:
63205
Cov.:
35
AF XY:
0.290
AC XY:
210262
AN XY:
725646
show subpopulations
Gnomad4 AFR exome
AF:
0.525
Gnomad4 AMR exome
AF:
0.171
Gnomad4 ASJ exome
AF:
0.268
Gnomad4 EAS exome
AF:
0.453
Gnomad4 SAS exome
AF:
0.325
Gnomad4 FIN exome
AF:
0.340
Gnomad4 NFE exome
AF:
0.274
Gnomad4 OTH exome
AF:
0.307
GnomAD4 genome
AF:
0.352
AC:
53424
AN:
151926
Hom.:
10337
Cov.:
32
AF XY:
0.350
AC XY:
26005
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.516
Gnomad4 AMR
AF:
0.216
Gnomad4 ASJ
AF:
0.257
Gnomad4 EAS
AF:
0.424
Gnomad4 SAS
AF:
0.327
Gnomad4 FIN
AF:
0.333
Gnomad4 NFE
AF:
0.287
Gnomad4 OTH
AF:
0.332
Alfa
AF:
0.298
Hom.:
3060
Bravo
AF:
0.350
Asia WGS
AF:
0.387
AC:
1350
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 07, 2014- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 21, 2013*15T>C in exon 20 of CCDC40: This variant is not expected to have clinical signi ficance because it has been identified in 49.7% (1929/3880) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs2304853). -
Primary ciliary dyskinesia 15 Benign:3
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -
Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Glycogen storage disease, type II Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.64
DANN
Benign
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2304853; hg19: chr17-78073589; COSMIC: COSV56408051; COSMIC: COSV56408051; API