17-80037932-G-T

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.30-191G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 548,826 control chromosomes in the GnomAD database, including 5,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1274 hom., cov: 31)
  • Exomes 𝑓: 0.13 (3775 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.213

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=-0.88).
• BP6: Variant 17-80037932-G-T is Benign according to our data. Variant chr17-80037932-G-T is described in ClinVar as [Benign]. Clinvar id is 1269480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.30-191G>T		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.30-191G>T		intron_variant
CCDC40	NM_001330508.2	c.30-191G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.30-191G>T		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19047 AN: 151632 Hom.: 1276 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.132 AC: 52513 AN: 397074 Hom.: 3775 Cov.: 3 AF XY: 0.133 AC XY: 28439 AN XY: 213670

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0717

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.126 AC: 19045 AN: 151752 Hom.: 1274 Cov.: 31 AF XY: 0.127 AC XY: 9380 AN XY: 74140

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.127

Alfa AF: 0.135 Hom.: 324

Bravo AF: 0.117

Asia WGS AF: 0.128 AC: 446 AN: 3478

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	-0.88
Cadd	Benign	5.0
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3764439; hg19: chr17-78011731;