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

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000289689 (HGNC:):

ENSG00000289689 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.1562+33G>A	intron_variant	Intron 10 of 19	ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 link	c.1562+33G>A	intron_variant	Intron 10 of 17		NP_001230271.1	Q4G0X9-2
CCDC40	NM_001330508.2 link	c.1562+33G>A	intron_variant	Intron 10 of 10		NP_001317437.1	Q4G0X9-4
LOC124904074	XR_007065931.1 link	n.305+5593C>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 link	c.1562+33G>A		intron_variant	Intron 10 of 19	5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1

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

GnomAD3 exomes

AF:

0.0156

AC:

3786

AN:

242208

Hom.:

311

AF XY:

0.0122

AC XY:

1623

AN XY:

132772

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 SAS exome

AF:

0.000361

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

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.00923

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000314

Gnomad4 FIN exome

AF:

0.0000580

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0585

AC:

8915

AN:

152290

Hom.:

803

Cov.:

AF XY:

0.0568

AC XY:

4227

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0311

Hom.:

Bravo

AF:

0.0664

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.27

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over