Variant 17-80038066-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_017950.4(CCDC40):c.30-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,183,138 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 36 hom. )

Consequence

CCDC40
NM_017950.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0540

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-80038066-G-A is Benign according to our data. Variant chr17-80038066-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213195.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00617 (939/152152) while in subpopulation NFE AF= 0.0089 (605/67998). AF 95% confidence interval is 0.00831. There are 8 homozygotes in gnomad4. There are 486 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CCDC40	NM_017950.4 linkuse as main transcript	c.30-57G>A	intron_variant	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2 linkuse as main transcript	c.30-57G>A	intron_variant		NP_001230271.1
CCDC40	NM_001330508.2 linkuse as main transcript	c.30-57G>A	intron_variant		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.30-57G>A		intron_variant		5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.00617

AC:

938

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00890

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00779

AC:

8032

AN:

1030986

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

4088

AN XY:

531168

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.000396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00503

Gnomad4 FIN exome

AF:

0.0186

Gnomad4 NFE exome

AF:

0.00864

Gnomad4 OTH exome

AF:

0.00620

GnomAD4 genome

AF:

0.00617

AC:

939

AN:

152152

Hom.:

Cov.:

AF XY:

0.00653

AC XY:

486

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00354

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.00890

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00631

Hom.:

Bravo

AF:

0.00475

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.45

DANN

Benign

0.49

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