Variant NM_000492.4:c.166G>A


Variant details:
Name NM_000492.4:c.166G>A
Protein name NP_000483.3:p.(Glu56Lys)
Genomic name (hg19) chr7:g.117149089G>A    UCSC    gnomAD
#Exon/intron exon 3
Legacy Name E56K
Class disease-causing
Subclass varying clinical consequence
WT sequence GTCCCACTTTTTATTCTTTTGCAGA G AATGGGATAGAGAGCTGGCTTCAAA
Mutant sequence GTCCCACTTTTTATTCTTTTGCAGA A AATGGGATAGAGAGCTGGCTTCAAA


External sources:
dbSNP
rs397508256


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Van Goor et al, 2014 23891399 ✓ ✓ ✓


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


Response to modulators:


Modulator FDA approval EMA approval in vitro / ex vivo data clinical data
IVA yesnoyesno
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C15 0.08223 0.05 0.998
VUS1 VUS2 VUS4 VUS5

Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 10
Asymptomatic compound heterozygote 1
CFTR-RD9
  • Aquagenic palmoplantar keratoderma  1
  • CBAVD  5
  • Other  1
  • Pancreatitis  2



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 5821heterozygoteCF-causing- Undef
CBAVD 5173heterozygoteCF-causing - Trans
VUS1 - Trans
CBAVD 5176heterozygoteCF-causing- Undef
CBAVD 2774heterozygoteVUS3- Undef
CBAVD 4311heterozygoteCF-causing- Undef
Aquagenic palmoplantar keratoderma 5304heterozygoteCFTR-RD-causing- Undef
Other 4927heterozygoteCFTR-RD-causing- Undef
Pancreatitis 5160heterozygoteCF-causing - Trans
VUS3- Undef
Pancreatitis 3163heterozygoteCFTR-RD-causing - Trans
Asymptomatic compound heterozygote 5166heterozygoteCF-causing - Trans


Color code:   non disease-causing <   VUS1 <   VUS2 <   VUS3 <   VUS4 <   VUS5 <   disease-causing



            CFTR variants are clustered into five groups:
  • 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.