NM_017950.4:c.2833-2445G>A

Variant names:

• chr17-80092818-G-A
• rs2361701
• NM_017950.4:c.2833-2445G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017950.4(CCDC40):​c.2833-2445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,034 control chromosomes in the GnomAD database, including 5,651 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5651 hom., cov: 32)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.2833-2445G>A		intron_variant	Intron 17 of 19	ENST00000397545.9	NP_060420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.2833-2445G>A		intron_variant	Intron 17 of 19	5	NM_017950.4	ENSP00000380679.4
CCDC40	ENST00000574799.5	n.2370-2445G>A		intron_variant	Intron 13 of 15	1
CCDC40	ENST00000572253.5	n.3084-2445G>A		intron_variant	Intron 4 of 5	2
CCDC40	ENST00000575431.1	n.477-2445G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38278 AN: 151916 Hom.: 5640 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38330 AN: 152034 Hom.: 5651 Cov.: 32 AF XY: 0.250 AC XY: 18564 AN XY: 74286

African (AFR) AF: 0.420 AC: 17428 AN: 41446

American (AMR) AF: 0.150 AC: 2287 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3466

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5172

South Asian (SAS) AF: 0.194 AC: 932 AN: 4816

European-Finnish (FIN) AF: 0.234 AC: 2467 AN: 10562

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12560 AN: 67966

Other (OTH) AF: 0.227 AC: 478 AN: 2110

Alfa AF: 0.209 Hom.: 10687

Bravo AF: 0.255

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2361701; hg19: chr17-78066617;