17-80038066-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017950.4(CCDC40):c.30-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,183,138 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (36 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0540

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=-0.91).
• BP6: Variant 17-80038066-G-A is Benign according to our data. Variant chr17-80038066-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213195.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00617 (939/152152) while in subpopulation NFE AF= 0.0089 (605/67998). AF 95% confidence interval is 0.00831. There are 8 homozygotes in gnomad4. There are 486 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.30-57G>A		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.30-57G>A		intron_variant
CCDC40	NM_001330508.2	c.30-57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.30-57G>A		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.00617 AC: 938 AN: 152034 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00890

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00779 AC: 8032 AN: 1030986 Hom.: 36 Cov.: 13 AF XY: 0.00770 AC XY: 4088 AN XY: 531168

Gnomad4 AFR exome AF: 0.00153

Gnomad4 AMR exome AF: 0.00212

Gnomad4 ASJ exome AF: 0.000396

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00503

Gnomad4 FIN exome AF: 0.0186

Gnomad4 NFE exome AF: 0.00864

Gnomad4 OTH exome AF: 0.00620

GnomAD4 genome AF: 0.00617 AC: 939 AN: 152152 Hom.: 8 Cov.: 32 AF XY: 0.00653 AC XY: 486 AN XY: 74378

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00354

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.00890

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00631 Hom.: 2

Bravo AF: 0.00475

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.45
Dann	Benign	0.49

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: rs146081939; hg19: chr17-78011865;