NM_017950.4:c.-49C>G

Variant names:

• chr17-80036614-C-G
• rs3752042
• NM_017950.4:c.-49C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017950.4(CCDC40):​c.-49C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,234,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CCDC40 NM_017950.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• Publications: 0 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: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	NM_017950.4	MANE Select	c.-49C>G		upstream_gene	N/A	NP_060420.2
	CCDC40	NM_001243342.2		c.-49C>G		upstream_gene	N/A	NP_001230271.1
	CCDC40	NM_001330508.2		c.-49C>G		upstream_gene	N/A	NP_001317437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.-49C>G		upstream_gene	N/A	ENSP00000380679.4
	CCDC40	ENST00000374876.4	TSL:1	c.-49C>G		upstream_gene	N/A	ENSP00000364010.4
	CCDC40	ENST00000374877.7	TSL:5	c.-49C>G		upstream_gene	N/A	ENSP00000364011.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000162 AC: 2 AN: 1234238 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 601606

African (AFR) AF: 0.00 AC: 0 AN: 24790

American (AMR) AF: 0.00 AC: 0 AN: 12888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18560

East Asian (EAS) AF: 0.00 AC: 0 AN: 27954

South Asian (SAS) AF: 0.00 AC: 0 AN: 56246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1009026

Other (OTH) AF: 0.00 AC: 0 AN: 50828

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.69
PhyloP100		0.96
PromoterAI		-0.17	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3752042; hg19: chr17-78010413;