Variant 17-80097448-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017950.4(CCDC40):c.3180+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,606,880 control chromosomes in the GnomAD database, including 58,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8528 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50288 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.249

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:

CCDC40 (HGNC:):

CCDC40 links:

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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 17-80097448-A-G is Benign according to our data. Variant chr17-80097448-A-G is described in ClinVar as [Benign]. Clinvar id is 260972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 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.3180+45A>G		intron_variant		ENST00000397545.9	NP_060420.2	Q4G0X9-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.3180+45A>G	intron_variant		5	NM_017950.4	ENSP00000380679.4	Q4G0X9-1
CCDC40	ENST00000574799.5 linkuse as main transcript	n.2717+45A>G	intron_variant		1
CCDC40	ENST00000572253.5 linkuse as main transcript	n.3476A>G	non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48059

AN:

151850

Hom.:

8509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.285

GnomAD3 exomes

AF:

0.265

AC:

64650

AN:

244122

Hom.:

9123

AF XY:

0.267

AC XY:

35449

AN XY:

132840

show subpopulations

Gnomad AFR exome

AF:

0.493

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.284

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.258

AC:

375695

AN:

1454912

Hom.:

50288

Cov.:

AF XY:

0.259

AC XY:

187242

AN XY:

723598

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.317

AC:

48122

AN:

151968

Hom.:

8528

Cov.:

AF XY:

0.313

AC XY:

23280

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.485

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.288

Alfa

AF:

0.274

Hom.:

1102

Bravo

AF:

0.318

Asia WGS

AF:

0.309

AC:

1077

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

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.4

DANN

Benign

0.31

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