Variant chr17-80036627-C-T 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 17-80036627-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,427,846 control chromosomes in the GnomAD database, including 1,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 794 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 586 hom. )

Consequence

CCDC40
NM_017950.4 upstream_gene

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.220

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:

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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=-0.65).

BP6

Variant 17-80036627-C-T is Benign according to our data. Variant chr17-80036627-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	Effect	MANE	Protein
CCDC40	NM_017950.4 linkuse as main transcript	upstream_gene_variant	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2 linkuse as main transcript	upstream_gene_variant		NP_001230271.1
CCDC40	NM_001330508.2 linkuse as main transcript	upstream_gene_variant		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript			upstream_gene_variant		5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.0574

AC:

8736

AN:

152074

Hom.:

796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.0440

GnomAD3 exomes

AF:

0.00975

AC:

594

AN:

60900

Hom.:

AF XY:

0.00784

AC XY:

279

AN XY:

35592

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00360

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000748

Gnomad OTH exome

AF:

0.00995

GnomAD4 exome

AF:

0.00551

AC:

7027

AN:

1275664

Hom.:

586

Cov.:

AF XY:

0.00481

AC XY:

3003

AN XY:

624482

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.00232

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000249

Gnomad4 FIN exome

AF:

0.0000319

Gnomad4 NFE exome

AF:

0.000538

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0575

AC:

8748

AN:

152182

Hom.:

794

Cov.:

AF XY:

0.0559

AC XY:

4158

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.0652

Asia WGS

AF:

0.0100

AC:

AN:

3470

ClinVar

Significance: Benign/Likely 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 10, 2018	- -
Likely 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

Benign:1

Likely 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

-0.65

CADD

Benign

DANN

Benign

0.92

Splicing

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