rs78493584

chr17-80089904-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017950.4(CCDC40):c.2832+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,613,574 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (4 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.517

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=-0.91).
• BP6: Variant 17-80089904-G-A is Benign according to our data. Variant chr17-80089904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00476 (725/152386) while in subpopulation AFR AF= 0.0167 (693/41598). AF 95% confidence interval is 0.0156. There are 8 homozygotes in gnomad4. There are 345 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.2832+20G>A		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.2832+20G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.2832+20G>A		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 728 AN: 152268 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00123 AC: 304 AN: 248050 Hom.: 4 AF XY: 0.000861 AC XY: 116 AN XY: 134774

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000983

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000552 AC: 807 AN: 1461188 Hom.: 4 Cov.: 32 AF XY: 0.000483 AC XY: 351 AN XY: 726896

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152386 Hom.: 8 Cov.: 32 AF XY: 0.00463 AC XY: 345 AN XY: 74522

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00230 Hom.: 0

Bravo AF: 0.00535

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely 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 29, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.74
Dann	Benign	0.37

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: rs78493584; hg19: chr17-78063703; COSMIC: COSV66478962; COSMIC: COSV66478962;