rs3752042

Positions:

• chr17-80036614-C-A

Variant summary

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

The variant allele was found at a frequency of 0.127 in 1,385,998 control chromosomes in the GnomAD database, including 11,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1283 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10426 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.957

Genes affected

(HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-80036614-C-A is Benign according to our data. Variant chr17-80036614-C-A is described in ClinVar as [Benign]. Clinvar id is 260946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.80036614C>A		intergenic_region
CCDC40	NM_017950.4	c.-49C>A		upstream_gene_variant		ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.-49C>A		upstream_gene_variant			NP_001230271.1
CCDC40	NM_001330508.2	c.-49C>A		upstream_gene_variant			NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.-49C>A		upstream_gene_variant		5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19135 AN: 151972 Hom.: 1285 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.139 AC: 4042 AN: 28986 Hom.: 325 AF XY: 0.142 AC XY: 2513 AN XY: 17702

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.0711

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.210

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.128 AC: 157419 AN: 1233918 Hom.: 10426 Cov.: 30 AF XY: 0.128 AC XY: 76841 AN XY: 601464

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0759

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.126 AC: 19132 AN: 152080 Hom.: 1283 Cov.: 32 AF XY: 0.127 AC XY: 9435 AN XY: 74344

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.127

Alfa AF: 0.141 Hom.: 217

Bravo AF: 0.117

Asia WGS AF: 0.129 AC: 448 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3752042; hg19: chr17-78010413;