rs61998241

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.946G>A(p.Ala316Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,613,928 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 56 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 67 hom. )

Consequence

CCDC40
NM_017950.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.49

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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics, 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 (MetaRNN=0.0037271678).

BP6

Variant 17-80050070-G-A is Benign according to our data. Variant chr17-80050070-G-A is described in ClinVar as Benign. ClinVar VariationId is 260982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC40	NM_017950.4	MANE Select	c.946G>A	p.Ala316Thr	missense	Exon 7 of 20	NP_060420.2
CCDC40	NM_001243342.2		c.946G>A	p.Ala316Thr	missense	Exon 7 of 18	NP_001230271.1	Q4G0X9-2
CCDC40	NM_001330508.2		c.946G>A	p.Ala316Thr	missense	Exon 7 of 11	NP_001317437.1	Q4G0X9-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.946G>A	p.Ala316Thr	missense	Exon 7 of 20	ENSP00000380679.4	Q4G0X9-1
CCDC40	ENST00000374876.4	TSL:1	c.946G>A	p.Ala316Thr	missense	Exon 7 of 9	ENSP00000364010.4	Q4G0X9-5
CCDC40	ENST00000574799.5	TSL:1	n.483G>A		non_coding_transcript_exon	Exon 3 of 16

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2365

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00409

AC:

1021

AN:

249392

AF XY:

0.00337

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00158

AC:

2313

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1028

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0533

AC:

1785

AN:

33472

American (AMR)

AF:

0.00320

AC:

143

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000108

AC:

120

AN:

1112002

Other (OTH)

AF:

0.00371

AC:

224

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

149

298

447

596

745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0156

AC:

2375

AN:

152082

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1092

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0544

AC:

2258

AN:

41484

American (AMR)

AF:

0.00523

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.000623

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67972

Other (OTH)

AF:

0.0128

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

108

215

323

430

538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00528

Hom.:

Bravo

AF:

0.0180

ESP6500AA

AF:

0.0544

AC:

222

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.00508

AC:

614

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 15 (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

PhyloP100

3.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.1

REVEL

Benign

0.17

Sift

Uncertain

0.011

Sift4G

Benign

0.17

Polyphen

0.70

Vest4

0.49

MVP

0.54

MPC

0.25

ClinPred

0.027

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.053

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over