17-80036749-C-A

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.29+58C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,444,646 control chromosomes in the GnomAD database, including 42,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3471 hom., cov: 31)
  • Exomes 𝑓: 0.24 (38872 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.164

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=-0.75).
• BP6: Variant 17-80036749-C-A is Benign according to our data. Variant chr17-80036749-C-A is described in ClinVar as [Benign]. Clinvar id is 1225552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.29+58C>A		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.29+58C>A		intron_variant
CCDC40	NM_001330508.2	c.29+58C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.29+58C>A		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29237 AN: 152040 Hom.: 3465 Cov.: 31

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.242 AC: 312137 AN: 1292490 Hom.: 38872 Cov.: 25 AF XY: 0.242 AC XY: 153276 AN XY: 634380

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.192 AC: 29260 AN: 152156 Hom.: 3471 Cov.: 31 AF XY: 0.193 AC XY: 14360 AN XY: 74402

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.222

Alfa AF: 0.215 Hom.: 734

Bravo AF: 0.196

Asia WGS AF: 0.286 AC: 993 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	-0.75
Cadd	Benign	7.7
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3752041; hg19: chr17-78010548; COSMIC: COSV53899748; COSMIC: COSV53899748;