17-80037892-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017950.4(CCDC40):c.30-231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 438,924 control chromosomes in the GnomAD database, including 15,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7244 hom., cov: 29)
  • Exomes 𝑓: 0.23 (8075 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.686

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-80037892-A-G is Benign according to our data. Variant chr17-80037892-A-G is described in ClinVar as [Benign]. Clinvar id is 1262578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.30-231A>G		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.30-231A>G		intron_variant
CCDC40	NM_001330508.2	c.30-231A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.30-231A>G		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43503 AN: 151202 Hom.: 7243 Cov.: 29

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.230 AC: 66060 AN: 287604 Hom.: 8075 AF XY: 0.227 AC XY: 35119 AN XY: 155022

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.288 AC: 43530 AN: 151320 Hom.: 7244 Cov.: 29 AF XY: 0.286 AC XY: 21116 AN XY: 73902

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.264

Alfa AF: 0.278 Hom.: 806

Bravo AF: 0.287

Asia WGS AF: 0.183 AC: 638 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.54
Dann	Benign	0.42

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: rs3764440; hg19: chr17-78011691;