dbSNP rs117419007: CCDC40:p.Ser210Ser (chr17-80047356-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_017950.4(CCDC40):c.630C>T(p.Ser210Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 1,613,620 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 41 hom. )

Consequence

CCDC40
NM_017950.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 0.244

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:

ENSG00000289689 (HGNC:):

ENSG00000289689 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 17-80047356-C-T is Benign according to our data. Variant chr17-80047356-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 197317.

BP7

Synonymous conserved (PhyloP=0.244 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00478 (728/152296) while in subpopulation NFE AF = 0.00566 (385/68018). AF 95% confidence interval is 0.00519. There are 5 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

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
CCDC40	NM_017950.4	MANE Select	c.630C>T	p.Ser210Ser	synonymous	Exon 4 of 20	NP_060420.2
CCDC40	NM_001243342.2		c.630C>T	p.Ser210Ser	synonymous	Exon 4 of 18	NP_001230271.1
CCDC40	NM_001330508.2		c.630C>T	p.Ser210Ser	synonymous	Exon 4 of 11	NP_001317437.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.630C>T	p.Ser210Ser	synonymous	Exon 4 of 20	ENSP00000380679.4
CCDC40	ENST00000374876.4	TSL:1	c.630C>T	p.Ser210Ser	synonymous	Exon 4 of 9	ENSP00000364010.4
CCDC40	ENST00000897784.1		c.630C>T	p.Ser210Ser	synonymous	Exon 4 of 21	ENSP00000567843.1

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

727

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00635

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00564

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00598

AC:

1484

AN:

248064

AF XY:

0.00603

show subpopulations

Gnomad AFR exome

AF:

0.000976

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00628

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0219

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00604

AC:

8821

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

4388

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33478

American (AMR)

AF:

0.00298

AC:

133

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00597

AC:

156

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00517

AC:

446

AN:

86202

European-Finnish (FIN)

AF:

0.0224

AC:

1189

AN:

53192

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00587

AC:

6526

AN:

1111798

Other (OTH)

AF:

0.00528

AC:

319

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

442

884

1325

1767

2209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.00478

AC:

728

AN:

152296

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

368

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41570

American (AMR)

AF:

0.00346

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00635

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00476

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0179

AC:

190

AN:

10610

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00566

AC:

385

AN:

68018

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00517

Hom.:

Bravo

AF:

0.00356

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00474

EpiControl

AF:

0.00540

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Primary ciliary dyskinesia (2)

Primary ciliary dyskinesia 15 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.9

(source)

DANN

Uncertain

0.98

PhyloP100

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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