rs8074956

chr17-80038204-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017950.4(CCDC40):c.93+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,524,936 control chromosomes in the GnomAD database, including 1,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (800 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (650 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 17-80038204-C-A is Benign according to our data. Variant chr17-80038204-C-A is described in ClinVar as [Benign]. Clinvar id is 260981.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	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.93+18C>A		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.93+18C>A		intron_variant
CCDC40	NM_001330508.2	c.93+18C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.93+18C>A		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8824 AN: 152120 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0445

GnomAD3 exomes AF: 0.0155 AC: 3812 AN: 245702 Hom.: 302 AF XY: 0.0125 AC XY: 1671 AN XY: 133390

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00254

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0105

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000734

Gnomad OTH exome AF: 0.00950

GnomAD4 exome AF: 0.00647 AC: 8887 AN: 1372698 Hom.: 650 Cov.: 21 AF XY: 0.00595 AC XY: 4090 AN XY: 687596

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.00229

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00918

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000571

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.0580 AC: 8836 AN: 152238 Hom.: 800 Cov.: 32 AF XY: 0.0565 AC XY: 4203 AN XY: 74454

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00952

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0103 Hom.: 147

Bravo AF: 0.0656

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.094
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs8074956; hg19: chr17-78012003;