dbSNP rs1467979: CCDC40:c.2450-663C>T (chr17-80086944-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017950.4(CCDC40):c.2450-663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 164,030 control chromosomes in the GnomAD database, including 5,900 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5684 hom., cov: 31)

Exomes 𝑓: 0.17 ( 216 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.2450-663C>T		intron_variant	Intron 14 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2 link	c.2450-663C>T		intron_variant	Intron 14 of 17		NP_001230271.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CCDC40	ENST00000397545.9 link	c.2450-663C>T	intron_variant	Intron 14 of 19	5	NM_017950.4	ENSP00000380679.4
CCDC40	ENST00000574799.5 link	n.1987-663C>T	intron_variant	Intron 10 of 15	1
CCDC40	ENST00000572253.5 link	n.1804C>T	non_coding_transcript_exon_variant	Exon 3 of 6	2
CCDC40	ENST00000374877.7 link	c.2450-663C>T	intron_variant	Intron 14 of 17	5		ENSP00000364011.3

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38158

AN:

151840

Hom.:

5673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.167

AC:

2019

AN:

12072

Hom.:

216

Cov.:

AF XY:

0.169

AC XY:

1066

AN XY:

6290

show subpopulations

African (AFR)

AF:

0.313

AC:

AN:

128

American (AMR)

AF:

0.117

AC:

326

AN:

2784

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

AN:

East Asian (EAS)

AF:

0.226

AC:

186

AN:

824

South Asian (SAS)

AF:

0.200

AC:

326

AN:

1628

European-Finnish (FIN)

AF:

0.211

AC:

AN:

166

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.168

AC:

1004

AN:

5988

Other (OTH)

AF:

0.194

AC:

AN:

480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.251

AC:

38208

AN:

151958

Hom.:

5684

Cov.:

AF XY:

0.249

AC XY:

18484

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.422

AC:

17509

AN:

41464

American (AMR)

AF:

0.148

AC:

2258

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

622

AN:

3470

East Asian (EAS)

AF:

0.218

AC:

1119

AN:

5140

South Asian (SAS)

AF:

0.193

AC:

927

AN:

4806

European-Finnish (FIN)

AF:

0.234

AC:

2471

AN:

10578

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12520

AN:

67926

Other (OTH)

AF:

0.224

AC:

471

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1388

2776

4163

5551

6939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.233

Hom.:

4747

Bravo

AF:

0.254

Asia WGS

AF:

0.230

AC:

799

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.35

(source)

DANN

Benign

0.33

PhyloP100

-1.9

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

Computational scores

Splicing

Publications

Other links and lift over