chr17-80039925-G-C

Position:

chr17-80039925-G-C

Variant summary

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

The NM_017950.4(CCDC40):c.207G>C(p.Val69Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 1,613,522 control chromosomes in the GnomAD database, including 778,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 73734 hom., cov: 28)

Exomes 𝑓: 0.98 ( 704889 hom. )

Consequence

CCDC40
NM_017950.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.77

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=-1.01).

BP6

Variant 17-80039925-G-C is Benign according to our data. Variant chr17-80039925-G-C is described in ClinVar as [Benign]. Clinvar id is 166807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80039925-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.207G>C	p.Val69Val	synonymous_variant	3/20	ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 link	c.207G>C	p.Val69Val	synonymous_variant	3/18		NP_001230271.1	Q4G0X9-2
CCDC40	NM_001330508.2 link	c.207G>C	p.Val69Val	synonymous_variant	3/11		NP_001317437.1	Q4G0X9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 link	c.207G>C	p.Val69Val	synonymous_variant	3/20	5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.985

AC:

149504

AN:

151774

Hom.:

73676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.993

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

0.984

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.979

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.991

GnomAD3 exomes

AF:

0.970

AC:

239634

AN:

247120

Hom.:

116331

AF XY:

0.969

AC XY:

130070

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.994

Gnomad AMR exome

AF:

0.965

Gnomad ASJ exome

AF:

0.983

Gnomad EAS exome

AF:

0.906

Gnomad SAS exome

AF:

0.915

Gnomad FIN exome

AF:

0.978

Gnomad NFE exome

AF:

0.990

Gnomad OTH exome

AF:

0.979

GnomAD4 exome

AF:

0.982

AC:

1434859

AN:

1461630

Hom.:

704889

Cov.:

AF XY:

0.980

AC XY:

712602

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.994

Gnomad4 AMR exome

AF:

0.969

Gnomad4 ASJ exome

AF:

0.983

Gnomad4 EAS exome

AF:

0.888

Gnomad4 SAS exome

AF:

0.915

Gnomad4 FIN exome

AF:

0.979

Gnomad4 NFE exome

AF:

0.991

Gnomad4 OTH exome

AF:

0.979

GnomAD4 genome

AF:

0.985

AC:

149621

AN:

151892

Hom.:

73734

Cov.:

AF XY:

0.983

AC XY:

72934

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.993

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

0.984

Gnomad4 EAS

AF:

0.905

Gnomad4 SAS

AF:

0.909

Gnomad4 FIN

AF:

0.979

Gnomad4 NFE

AF:

0.991

Gnomad4 OTH

AF:

0.991

Alfa

AF:

0.989

Hom.:

18343

Bravo

AF:

0.987

Asia WGS

AF:

0.903

AC:

3142

AN:

3478

EpiCase

AF:

0.993

EpiControl

AF:

0.992

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 05, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Val69Val in exon 3 of CCDC40: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.7% (56/8354) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs2289527). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 15

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.080

DANN

Benign

0.48

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