Updates for c.1666A>G:
2015-07-03 class changed from unclassified to disease-causing
2024-08-01 subclass updated from CFTR-RD-causing to non disease-causing
2024-12-09 Variant classified as non-disease-causing on the basis of epidemiological data (in particular high frequency in the general population), the number and type of diagnosis for patients reported in CFTR-France and functional data




Variant NM_000492.4:c.1666A>G


Variant details:
Name NM_000492.4:c.1666A>G
Protein name NP_000483.3:p.(Ile556Val)
Genomic name (hg19)     chr7:g.117227874A>G    UCSC    
Genomic name (hg38) chr7:g.117587820A>G    UCSC
#Exon/intron exon 12
Legacy Name I556V
Class non disease-causing
Subclass NULL
WT sequence ACTGAGTGGAGGTCAACGAGCAAGA A TTTCTTTAGCAAGGTGAATAACTAA
Mutant sequence ACTGAGTGGAGGTCAACGAGCAAGA G TTTCTTTAGCAAGGTGAATAACTAA

Other databases:

Not found		dbSNP
rs75789129



Pathogenicity predictors:

Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Lee et al, 2003 12952861 ✓ ✓ ✓


« ✓ » indicates the type of analysis performed and not the results



1 individuals carrying this variant are reported in CFTR-NGS catalogue


3 patients carrying this variant are reported in CFTR-France:

TOTAL NUMBER OF PATIENTS 3
Asymptomatic compound heterozygote 1
CFTR-RD2
  • CBAVD  1
  • Pancreatitis  1




Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing

Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Asymptomatic compound heterozygote 4685heterozygoteCF-causing - Trans
CBAVD 1345heterozygoteCFTR-RD-causing- Undef
Pancreatitis 5152homozygote


Color code:   non disease-causing <   likely benign <   VUS <   likely pathogenic <   disease-causing



            CFTR variants are clustered into five groups (click here for more details about the classification of variants):
  • CF-causing: when in trans with another CF-causing mutation, will result in CF.
  • CFTR-RD causing: when in trans with a CF-causing mutation, will result in CFTR-related disorders (CFTR-RD) such as chronic pancreatitis, bronchiectasis, CRS-NP (chronic rhinosinusitis with or without nasal polyposis) or CBAVD (congenital absence of vas deferens), according to Bombieri C et al., 2011.
  • Varying clinical consequence: when in trans with another CF-causing mutation, can either result in CF or in a CFTR-RD.
  • Non disease-causing: when in trans with a CF-causing mutation, will not cause CF, nor CFTR-RD.
  • VUS (Variant of unknown clinical significance): unclassified because of insufficient data.



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