Genetic Variant CCDC40:c.553-41A>G (chr17-80047238-A-G) – 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.553-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,599,436 control chromosomes in the GnomAD database, including 56,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 11348 hom., cov: 33)

Exomes 𝑓: 0.24 ( 44653 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.17

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=-0.92).

BP6

Variant 17-80047238-A-G is Benign according to our data. Variant chr17-80047238-A-G is described in ClinVar as [Benign]. Clinvar id is 260976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4 link	c.553-41A>G	intron_variant	Intron 3 of 19	ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 link	c.553-41A>G	intron_variant	Intron 3 of 17		NP_001230271.1	Q4G0X9-2
CCDC40	NM_001330508.2 link	c.553-41A>G	intron_variant	Intron 3 of 10		NP_001317437.1	Q4G0X9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 link	c.553-41A>G		intron_variant	Intron 3 of 19	5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51615

AN:

152096

Hom.:

11327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.248

AC:

61491

AN:

247566

Hom.:

9319

AF XY:

0.249

AC XY:

33417

AN XY:

134470

show subpopulations

Gnomad AFR exome

AF:

0.643

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.163

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.238

AC:

343813

AN:

1447222

Hom.:

44653

Cov.:

AF XY:

0.238

AC XY:

171725

AN XY:

720824

show subpopulations

Gnomad4 AFR exome

AF:

0.632

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.340

AC:

51688

AN:

152214

Hom.:

11348

Cov.:

AF XY:

0.336

AC XY:

25039

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.628

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.290

Hom.:

1429

Bravo

AF:

0.343

Asia WGS

AF:

0.233

AC:

814

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 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

- -

Primary ciliary dyskinesia 15

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.92

CADD

Benign

0.052

DANN

Benign

0.41

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