Variant rs74000392 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.3022-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,222 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 96 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 225 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.587

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=-0.85).

BP6

Variant 17-80097217-G-A is Benign according to our data. Variant chr17-80097217-G-A is described in ClinVar as [Benign]. Clinvar id is 260967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0617 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.3022-28G>A		intron_variant		ENST00000397545.9	NP_060420.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.3022-28G>A	intron_variant	5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1
CCDC40	ENST00000574799.5 linkuse as main transcript	n.2559-28G>A	intron_variant, non_coding_transcript_variant	1
CCDC40	ENST00000572253.5 linkuse as main transcript	n.3273-28G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3613

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.0302

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0149

AC:

3722

AN:

249008

Hom.:

AF XY:

0.0148

AC XY:

2000

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.0690

Gnomad AMR exome

AF:

0.00519

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0475

Gnomad SAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00542

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00971

AC:

14179

AN:

1460934

Hom.:

225

Cov.:

AF XY:

0.0101

AC XY:

7333

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.00572

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0384

Gnomad4 SAS exome

AF:

0.0295

Gnomad4 FIN exome

AF:

0.000983

Gnomad4 NFE exome

AF:

0.00586

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0238

AC:

3619

AN:

152288

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1752

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0637

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0514

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00351

Hom.:

Bravo

AF:

0.0265

Asia WGS

AF:

0.0450

AC:

159

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 14, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.3

DANN

Benign

0.78

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