rs7212525

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017950.4(CCDC40):c.676+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,607,888 control chromosomes in the GnomAD database, including 56,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 11318 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45352 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.10

Publications

10 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:

ENSG00000289689 (HGNC:):

ENSG00000289689 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-80047415-T-C is Benign according to our data. Variant chr17-80047415-T-C is described in ClinVar as Benign. ClinVar VariationId is 178707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.676+13T>C	intron_variant	Intron 4 of 19	ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 link	c.676+13T>C	intron_variant	Intron 4 of 17		NP_001230271.1	Q4G0X9-2
CCDC40	NM_001330508.2 link	c.676+13T>C	intron_variant	Intron 4 of 10		NP_001317437.1	Q4G0X9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 link	c.676+13T>C		intron_variant	Intron 4 of 19	5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51547

AN:

151974

Hom.:

11296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.627

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.246

AC:

58669

AN:

238144

AF XY:

0.247

show subpopulations

Gnomad AFR exome

AF:

0.640

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.240

AC:

349238

AN:

1455796

Hom.:

45352

Cov.:

AF XY:

0.240

AC XY:

173865

AN XY:

723964

show subpopulations

African (AFR)

AF:

0.635

AC:

21193

AN:

33384

American (AMR)

AF:

0.141

AC:

6249

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

5981

AN:

26010

East Asian (EAS)

AF:

0.182

AC:

7220

AN:

39570

South Asian (SAS)

AF:

0.255

AC:

21870

AN:

85608

European-Finnish (FIN)

AF:

0.284

AC:

14787

AN:

52134

Middle Eastern (MID)

AF:

0.274

AC:

1470

AN:

5368

European-Non Finnish (NFE)

AF:

0.230

AC:

255386

AN:

1109360

Other (OTH)

AF:

0.251

AC:

15082

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13299

26598

39897

53196

66495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8866

17732

26598

35464

44330

<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:

0.339

AC:

51621

AN:

152092

Hom.:

11318

Cov.:

AF XY:

0.336

AC XY:

25026

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.628

AC:

26038

AN:

41484

American (AMR)

AF:

0.188

AC:

2876

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

821

AN:

3468

East Asian (EAS)

AF:

0.165

AC:

853

AN:

5168

South Asian (SAS)

AF:

0.237

AC:

1142

AN:

4820

European-Finnish (FIN)

AF:

0.275

AC:

2900

AN:

10564

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16156

AN:

67984

Other (OTH)

AF:

0.302

AC:

637

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1514

3028

4542

6056

7570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.298

Hom.:

1568

Bravo

AF:

0.343

Asia WGS

AF:

0.233

AC:

814

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

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

676+13T>C in intron 4 of CCDC40: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence. It has been identified in 40.2% (1665/4138) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs7212525). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 15

Benign:3

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.91

CADD

Benign

0.67

(source)

DANN

Benign

0.17

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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