rs1467979

Variant names:

• chr17-80086944-C-T
• rs1467979
• NM_017950.4:c.2450-663C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	NM_017950.4	MANE Select	c.2450-663C>T		intron	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.2450-663C>T		intron	N/A	NP_001230271.1	Q4G0X9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.2450-663C>T		intron	N/A	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.1987-663C>T		intron	N/A
	CCDC40	ENST00000897784.1		c.2450-663C>T		intron	N/A	ENSP00000567843.1

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

African (AFR) AF: 0.313 AC: 40 AN: 128

American (AMR) AF: 0.117 AC: 326 AN: 2784

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 7 AN: 66

East Asian (EAS) AF: 0.226 AC: 186 AN: 824

South Asian (SAS) AF: 0.200 AC: 326 AN: 1628

European-Finnish (FIN) AF: 0.211 AC: 35 AN: 166

Middle Eastern (MID) AF: 0.250 AC: 2 AN: 8

European-Non Finnish (NFE) AF: 0.168 AC: 1004 AN: 5988

Other (OTH) AF: 0.194 AC: 93 AN: 480

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

African (AFR) AF: 0.422 AC: 17509 AN: 41464

American (AMR) AF: 0.148 AC: 2258 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1119 AN: 5140

South Asian (SAS) AF: 0.193 AC: 927 AN: 4806

European-Finnish (FIN) AF: 0.234 AC: 2471 AN: 10578

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12520 AN: 67926

Other (OTH) AF: 0.224 AC: 471 AN: 2106

Alfa AF: 0.233 Hom.: 4747

Bravo AF: 0.254

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.33
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1467979; hg19: chr17-78060743;