Variant rs139301500 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_017950.4(CCDC40):c.3021+24_3021+25delAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,610,074 control chromosomes in the GnomAD database, including 679 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 38 hom., cov: 33)

Exomes 𝑓: 0.028 ( 641 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.641

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 -16 ACMG points.

BP6

Variant 17-80095474-CAG-C is Benign according to our data. Variant chr17-80095474-CAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 260966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0209 (3187/152372) while in subpopulation NFE AF= 0.03 (2041/68036). AF 95% confidence interval is 0.0289. There are 38 homozygotes in gnomad4. There are 1525 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4 linkuse as main transcript	c.3021+24_3021+25delAG		intron_variant		ENST00000397545.9	NP_060420.2	Q4G0X9-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.3021+24_3021+25delAG	intron_variant	5	NM_017950.4	ENSP00000380679.4	Q4G0X9-1
CCDC40	ENST00000574799.5 linkuse as main transcript	n.2558+24_2558+25delAG	intron_variant	1
CCDC40	ENST00000572253.5 linkuse as main transcript	n.3272+24_3272+25delAG	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3187

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00603

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0318

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0300

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0225

AC:

5480

AN:

243968

Hom.:

AF XY:

0.0229

AC XY:

3043

AN XY:

132956

show subpopulations

Gnomad AFR exome

AF:

0.00448

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0343

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0268

GnomAD4 exome

AF:

0.0285

AC:

41536

AN:

1457702

Hom.:

641

AF XY:

0.0280

AC XY:

20307

AN XY:

725368

show subpopulations

Gnomad4 AFR exome

AF:

0.00482

Gnomad4 AMR exome

AF:

0.0138

Gnomad4 ASJ exome

AF:

0.0356

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.0355

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0262

GnomAD4 genome

AF:

0.0209

AC:

3187

AN:

152372

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1525

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00601

Gnomad4 AMR

AF:

0.0215

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.0318

Gnomad4 NFE

AF:

0.0300

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0276

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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