NM_017950.4:c.2832+462_2832+463insCAC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017950.4(CCDC40):c.2832+462_2832+463insCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 426,652 control chromosomes in the GnomAD database, including 945 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 68 hom., cov: 0)

Exomes 𝑓: 0.032 ( 877 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0180

Publications

7 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 -16 ACMG points.

BP6

Variant 17-80090346-A-ACAC is Benign according to our data. Variant chr17-80090346-A-ACAC is described in ClinVar as Benign. ClinVar VariationId is 218550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.2832+462_2832+463insCAC		intron_variant	Intron 17 of 19	ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 link	c.3040_3041insCAC	p.Thr1013dup	disruptive_inframe_insertion	Exon 18 of 18		NP_001230271.1	Q4G0X9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 link	c.2832+462_2832+463insCAC		intron_variant	Intron 17 of 19	5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

567

AN:

19316

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.0301

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.0219

Gnomad SAS

AF:

0.0649

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0362

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.295

AC:

19150

AN:

65002

AF XY:

0.320

show subpopulations

Gnomad AFR exome

AF:

0.0947

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.0957

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.0324

AC:

13186

AN:

407314

Hom.:

877

Cov.:

AF XY:

0.0333

AC XY:

6912

AN XY:

207388

show subpopulations

African (AFR)

AF:

0.0583

AC:

713

AN:

12228

American (AMR)

AF:

0.0170

AC:

289

AN:

16960

Ashkenazi Jewish (ASJ)

AF:

0.0485

AC:

367

AN:

7562

East Asian (EAS)

AF:

0.0100

AC:

158

AN:

15764

South Asian (SAS)

AF:

0.0387

AC:

1116

AN:

28800

European-Finnish (FIN)

AF:

0.0447

AC:

688

AN:

15394

Middle Eastern (MID)

AF:

0.126

AC:

226

AN:

1794

European-Non Finnish (NFE)

AF:

0.0309

AC:

8951

AN:

289752

Other (OTH)

AF:

0.0356

AC:

678

AN:

19060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

388

776

1163

1551

1939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<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:

0.0294

AC:

568

AN:

19338

Hom.:

Cov.:

AF XY:

0.0305

AC XY:

291

AN XY:

9548

show subpopulations

African (AFR)

AF:

0.0253

AC:

158

AN:

6256

American (AMR)

AF:

0.0154

AC:

AN:

3192

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

AN:

270

East Asian (EAS)

AF:

0.0219

AC:

AN:

868

South Asian (SAS)

AF:

0.0659

AC:

AN:

364

European-Finnish (FIN)

AF:

0.0576

AC:

AN:

764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0361

AC:

260

AN:

7200

Other (OTH)

AF:

0.0164

AC:

AN:

244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 05, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.018

Mutation Taster

=83/17

polymorphism (auto)

(source)

Splicing

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