chr17-80081959-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017950.4(CCDC40):c.1890T>G(p.Ala630Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,613,186 control chromosomes in the GnomAD database, including 212,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20864 hom., cov: 30)

Exomes 𝑓: 0.51 ( 191388 hom. )

Consequence

CCDC40
NM_017950.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.81

Publications

14 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

CCDC40 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-80081959-T-G is Benign according to our data. Variant chr17-80081959-T-G is described in ClinVar as Benign. ClinVar VariationId is 162850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.1890T>G	p.Ala630Ala	synonymous_variant	Exon 12 of 20	ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 link	c.1890T>G	p.Ala630Ala	synonymous_variant	Exon 12 of 18		NP_001230271.1	Q4G0X9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC40	ENST00000397545.9 link	c.1890T>G	p.Ala630Ala	synonymous_variant	Exon 12 of 20	5	NM_017950.4	ENSP00000380679.4	Q4G0X9-1
CCDC40	ENST00000574799.5 link	n.1427T>G		non_coding_transcript_exon_variant	Exon 8 of 16	1
CCDC40	ENST00000374877.7 link	c.1890T>G	p.Ala630Ala	synonymous_variant	Exon 12 of 18	5		ENSP00000364011.3	Q4G0X9-2
CCDC40	ENST00000572253.5 link	n.517T>G		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78617

AN:

151548

Hom.:

20865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.589

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.522

Gnomad OTH

AF:

0.548

GnomAD2 exomes

AF:

0.481

AC:

119687

AN:

248586

AF XY:

0.487

show subpopulations

Gnomad AFR exome

AF:

0.589

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.523

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.508

AC:

743079

AN:

1461518

Hom.:

191388

Cov.:

AF XY:

0.508

AC XY:

369258

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.595

AC:

19909

AN:

33480

American (AMR)

AF:

0.392

AC:

17511

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

15764

AN:

26132

East Asian (EAS)

AF:

0.310

AC:

12300

AN:

39694

South Asian (SAS)

AF:

0.453

AC:

39072

AN:

86238

European-Finnish (FIN)

AF:

0.490

AC:

26169

AN:

53398

Middle Eastern (MID)

AF:

0.630

AC:

3635

AN:

5768

European-Non Finnish (NFE)

AF:

0.519

AC:

577342

AN:

1111726

Other (OTH)

AF:

0.520

AC:

31377

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

22598

45196

67793

90391

112989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16478

32956

49434

65912

82390

<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:

0.519

AC:

78647

AN:

151668

Hom.:

20864

Cov.:

AF XY:

0.512

AC XY:

37967

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.588

AC:

24353

AN:

41396

American (AMR)

AF:

0.428

AC:

6539

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2108

AN:

3470

East Asian (EAS)

AF:

0.279

AC:

1402

AN:

5032

South Asian (SAS)

AF:

0.430

AC:

2067

AN:

4812

European-Finnish (FIN)

AF:

0.486

AC:

5135

AN:

10556

Middle Eastern (MID)

AF:

0.651

AC:

190

AN:

292

European-Non Finnish (NFE)

AF:

0.522

AC:

35412

AN:

67830

Other (OTH)

AF:

0.543

AC:

1144

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1908

3816

5724

7632

9540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.513

Hom.:

16445

Bravo

AF:

0.518

Asia WGS

AF:

0.339

AC:

1184

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala630Ala in exon 12 of CCDC40: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 49.0% (4178/8520) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35578653). -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 15

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.30

(source)

DANN

Benign

0.34

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over