dbSNP rs10083858: CCDC40:c.1562+33G>A (chr17-80065639-G-A) – ACMG Classification: Benign (-20 pts)

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.1562+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,610,092 control chromosomes in the GnomAD database, including 1,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 803 hom., cov: 30)

Exomes 𝑓: 0.0067 ( 734 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.15

Publications

0 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 (BayesDel_noAF=-0.81).

BP6

Variant 17-80065639-G-A is Benign according to our data. Variant chr17-80065639-G-A is described in ClinVar as Benign. ClinVar VariationId is 260954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 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	Effect	Exon Rank	Protein	UniProt
CCDC40	NM_017950.4	MANE Select	c.1562+33G>A	intron	N/A	NP_060420.2
CCDC40	NM_001243342.2		c.1562+33G>A	intron	N/A	NP_001230271.1	Q4G0X9-2
CCDC40	NM_001330508.2		c.1562+33G>A	intron	N/A	NP_001317437.1	Q4G0X9-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.1562+33G>A	intron	N/A	ENSP00000380679.4	Q4G0X9-1
CCDC40	ENST00000374876.4	TSL:1	c.1318-444G>A	intron	N/A	ENSP00000364010.4	Q4G0X9-5
CCDC40	ENST00000574799.5	TSL:1	n.1099+33G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0585

AC:

8903

AN:

152174

Hom.:

804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.0465

GnomAD2 exomes

AF:

0.0156

AC:

3786

AN:

242208

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000484

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00669

AC:

9756

AN:

1457802

Hom.:

734

Cov.:

AF XY:

0.00591

AC XY:

4286

AN XY:

725254

show subpopulations

African (AFR)

AF:

0.202

AC:

6732

AN:

33404

American (AMR)

AF:

0.0145

AC:

647

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

241

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000314

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.0000580

AC:

AN:

51694

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

4472

European-Non Finnish (NFE)

AF:

0.00105

AC:

1164

AN:

1111566

Other (OTH)

AF:

0.0145

AC:

870

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

474

948

1422

1896

2370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

220

440

660

880

1100

<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:

0.0585

AC:

8915

AN:

152290

Hom.:

803

Cov.:

AF XY:

0.0568

AC XY:

4227

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.198

AC:

8241

AN:

41548

American (AMR)

AF:

0.0287

AC:

439

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00135

AC:

AN:

68036

Other (OTH)

AF:

0.0460

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

373

746

1119

1492

1865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0319

Hom.:

120

Bravo

AF:

0.0664

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.27

(source)

DANN

Benign

0.86

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over