rs3816257

Positions:

• chr17-80100647-A-C
• chr17-80100647-A-G
• chr17-80100647-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.315 in 150,078 control chromosomes in the GnomAD database, including 8,086 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8086 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.80100647A>C		intergenic_region
CCDC40	NM_017950.4	c.*872A>C		downstream_gene_variant		ENST00000397545.9	NP_060420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.*872A>C		downstream_gene_variant		5	NM_017950.4	ENSP00000380679.4
CCDC40	ENST00000574799.5	n.*43A>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47327 AN: 149968 Hom.: 8079 Cov.: 30

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.323

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.315 AC: 47345 AN: 150078 Hom.: 8086 Cov.: 30 AF XY: 0.312 AC XY: 22816 AN XY: 73032

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.324

Alfa AF: 0.369 Hom.: 12630

Bravo AF: 0.310

Asia WGS AF: 0.338 AC: 1177 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3816257; hg19: chr17-78074446;