17-80099763-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017950.4(CCDC40):c.3417A>G(p.Pro1139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,612,434 control chromosomes in the GnomAD database, including 171,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18977 hom., cov: 31)

Exomes 𝑓: 0.45 ( 152785 hom. )

Consequence

CCDC40
NM_017950.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-80099763-A-G is Benign according to our data. Variant chr17-80099763-A-G is described in ClinVar as [Benign]. Clinvar id is 178712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80099763-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.3417A>G	p.Pro1139Pro	synonymous_variant	Exon 20 of 20	ENST00000397545.9	NP_060420.2	Q4G0X9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 link	c.3417A>G	p.Pro1139Pro	synonymous_variant	Exon 20 of 20	5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1
CCDC40	ENST00000574799.5 link	n.2954A>G		non_coding_transcript_exon_variant	Exon 16 of 16	1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74666

AN:

151786

Hom.:

18954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.466

GnomAD3 exomes

AF:

0.451

AC:

111378

AN:

247100

Hom.:

26325

AF XY:

0.461

AC XY:

61985

AN XY:

134524

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.521

Gnomad FIN exome

AF:

0.536

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.454

AC:

662967

AN:

1460530

Hom.:

152785

Cov.:

AF XY:

0.457

AC XY:

331983

AN XY:

726564

show subpopulations

Gnomad4 AFR exome

AF:

0.615

Gnomad4 AMR exome

AF:

0.253

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.454

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.542

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.492

AC:

74734

AN:

151904

Hom.:

18977

Cov.:

AF XY:

0.491

AC XY:

36484

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.511

Gnomad4 FIN

AF:

0.542

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.450

Hom.:

22871

Bravo

AF:

0.479

EpiCase

AF:

0.454

EpiControl

AF:

0.453

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

May 07, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro1139Pro in exon 20 of CCDC40: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 44.7% (3724/8334) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2304854). -

Primary ciliary dyskinesia

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 15

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glycogen storage disease, type II

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.90

CADD

Benign

0.060

DANN

Benign

0.34

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

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