rs10083858

chr17-80065639-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017950.4(CCDC40):c.1562+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,610,092 control chromosomes in the GnomAD database, including 1,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (803 hom., cov: 30)
  • Exomes 𝑓: 0.0067 (734 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-80065639-G-A is Benign according to our data. Variant chr17-80065639-G-A is described in ClinVar as [Benign]. Clinvar id is 260954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.1562+33G>A		intron_variant		ENST00000397545.9
LOC124904074	XR_007065931.1	n.305+5593C>T		intron_variant, non_coding_transcript_variant
CCDC40	NM_001243342.2	c.1562+33G>A		intron_variant
CCDC40	NM_001330508.2	c.1562+33G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.1562+33G>A		intron_variant		5	NM_017950.4	P2
	ENST00000695611.1	n.313+5593C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0585 AC: 8903 AN: 152174 Hom.: 804 Cov.: 30

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.0465

GnomAD3 exomes AF: 0.0156 AC: 3786 AN: 242208 Hom.: 311 AF XY: 0.0122 AC XY: 1623 AN XY: 132772

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000361

Gnomad FIN exome AF: 0.0000484

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00669 AC: 9756 AN: 1457802 Hom.: 734 Cov.: 32 AF XY: 0.00591 AC XY: 4286 AN XY: 725254

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.00923

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000314

Gnomad4 FIN exome AF: 0.0000580

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0585 AC: 8915 AN: 152290 Hom.: 803 Cov.: 30 AF XY: 0.0568 AC XY: 4227 AN XY: 74456

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0287

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0311 Hom.: 60

Bravo AF: 0.0664

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.27
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10083858; hg19: chr17-78039438;