Variant chr17-80038204-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017950.4(CCDC40):c.93+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,524,936 control chromosomes in the GnomAD database, including 1,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 800 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 650 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.02

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 links:

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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=-0.97).

BP6

Variant 17-80038204-C-A is Benign according to our data. Variant chr17-80038204-C-A is described in ClinVar as [Benign]. Clinvar id is 260981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CCDC40	NM_017950.4 linkuse as main transcript	c.93+18C>A	intron_variant	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2 linkuse as main transcript	c.93+18C>A	intron_variant		NP_001230271.1
CCDC40	NM_001330508.2 linkuse as main transcript	c.93+18C>A	intron_variant		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.93+18C>A		intron_variant		5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8824

AN:

152120

Hom.:

802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0274

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0155

AC:

3812

AN:

245702

Hom.:

302

AF XY:

0.0125

AC XY:

1671

AN XY:

133390

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.00254

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0105

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000734

Gnomad OTH exome

AF:

0.00950

GnomAD4 exome

AF:

0.00647

AC:

8887

AN:

1372698

Hom.:

650

Cov.:

AF XY:

0.00595

AC XY:

4090

AN XY:

687596

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.00229

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00918

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000571

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.0580

AC:

8836

AN:

152238

Hom.:

800

Cov.:

AF XY:

0.0565

AC XY:

4203

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.0274

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00952

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0103

Hom.:

147

Bravo

AF:

0.0656

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

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 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.094

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over