17-80099556-A-G

Position:

chr17-80099556-A-G

Variant summary

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

The NM_017950.4(CCDC40):c.3210A>G(p.Thr1070=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,611,218 control chromosomes in the GnomAD database, including 73,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10236 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63158 hom. )

Consequence

CCDC40
NM_017950.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.62

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=-0.92).

BP6

Variant 17-80099556-A-G is Benign according to our data. Variant chr17-80099556-A-G is described in ClinVar as [Benign]. Clinvar id is 162852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80099556-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4 linkuse as main transcript	c.3210A>G	p.Thr1070=	synonymous_variant	20/20	ENST00000397545.9	NP_060420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.3210A>G	p.Thr1070=	synonymous_variant	20/20	5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1
CCDC40	ENST00000574799.5 linkuse as main transcript	n.2747A>G		non_coding_transcript_exon_variant	16/16	1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53166

AN:

151880

Hom.:

10219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.303

AC:

74940

AN:

247662

Hom.:

12200

AF XY:

0.305

AC XY:

41130

AN XY:

134636

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.409

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.288

AC:

420850

AN:

1459220

Hom.:

63158

Cov.:

AF XY:

0.290

AC XY:

210357

AN XY:

726066

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.453

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.350

AC:

53224

AN:

151998

Hom.:

10236

Cov.:

AF XY:

0.349

AC XY:

25909

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.298

Hom.:

2972

Bravo

AF:

0.348

Asia WGS

AF:

0.388

AC:

1351

AN:

3478

EpiCase

AF:

0.279

EpiControl

AF:

0.276

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Thr1070Thr 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 49.4% (1938/3920) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56407805). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 07, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 15

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	-	- -

Glycogen storage disease, type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.063

DANN

Benign

0.56

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