rs1467979

Positions:

• chr17-80086944-C-T

Variant summary

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

The NM_017950.4(CCDC40):​c.2450-663C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 164,030 control chromosomes in the GnomAD database, including 5,900 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 0.25 (5684 hom., cov: 31)
  • Exomes 𝑓: 0.17 (216 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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]

CCDC40 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.2450-663C>T		intron_variant		ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.2450-663C>T		intron_variant			NP_001230271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.2450-663C>T		intron_variant		5	NM_017950.4	ENSP00000380679.4
CCDC40	ENST00000574799.5	n.1987-663C>T		intron_variant		1
CCDC40	ENST00000374877.7	c.2450-663C>T		intron_variant		5		ENSP00000364011.3
CCDC40	ENST00000572253.5	n.1804C>T		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38158 AN: 151840 Hom.: 5673 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.167 AC: 2019 AN: 12072 Hom.: 216 Cov.: 0 AF XY: 0.169 AC XY: 1066 AN XY: 6290

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.251 AC: 38208 AN: 151958 Hom.: 5684 Cov.: 31 AF XY: 0.249 AC XY: 18484 AN XY: 74282

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.224

Alfa AF: 0.214 Hom.: 1507

Bravo AF: 0.254

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.33

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: rs1467979; hg19: chr17-78060743;