rs2289533

Positions:

chr17-80050295-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017950.4(CCDC40):c.1159+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,548,256 control chromosomes in the GnomAD database, including 45,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3592 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42085 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.684

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:

(HGNC:):

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=-0.8).

BP6

Variant 17-80050295-C-T is Benign according to our data. Variant chr17-80050295-C-T is described in ClinVar as [Benign]. Clinvar id is 162847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80050295-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CCDC40	NM_017950.4 linkuse as main transcript	c.1159+12C>T	intron_variant	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2 linkuse as main transcript	c.1159+12C>T	intron_variant		NP_001230271.1
CCDC40	NM_001330508.2 linkuse as main transcript	c.1159+12C>T	intron_variant		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.1159+12C>T		intron_variant		5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1
	ENST00000695611.1 linkuse as main transcript	n.1432-2776G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29749

AN:

152010

Hom.:

3587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0540

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.242

AC:

37159

AN:

153680

Hom.:

4956

AF XY:

0.238

AC XY:

19533

AN XY:

82190

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.303

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.402

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.241

AC:

337160

AN:

1396128

Hom.:

42085

Cov.:

AF XY:

0.241

AC XY:

166177

AN XY:

689096

show subpopulations

Gnomad4 AFR exome

AF:

0.0415

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.196

AC:

29769

AN:

152128

Hom.:

3592

Cov.:

AF XY:

0.199

AC XY:

14781

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0539

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.373

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.235

Hom.:

7698

Bravo

AF:

0.194

Asia WGS

AF:

0.290

AC:

1007

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	1159+12C>T in intron 7 of CCDC40: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 21.4% (1740/8114) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs2289533). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 15

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.0

DANN

Benign

0.67

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