Variant NM_000492.4:c.274G>A


Variant details:
Name NM_000492.4:c.274G>A
Protein name NP_000483.3:p.(Glu92Lys)
Genomic name (hg19) chr7:g.117170953G>A    UCSC    gnomAD
#Exon/intron exon 4
Legacy Name E92K
Class disease-causing
Subclass varying clinical consequence
WT sequence TTTCTCTGTTTTTCCCCTTTTGTAG G AAGTCACCAAAGCAGTACAGCCTCT
Mutant sequence TTTCTCTGTTTTTCCCCTTTTGTAG A AAGTCACCAAAGCAGTACAGCCTCT


External sources:
dbSNP
rs121908751


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Gene et al, 2008 18306312 ✓ ✓ ✓
Van Goor et al, 2014 23891399 ✓ ✓ ✓
Sosnay et al, 2013 23974870 ✓ ✓
Bergougnoux et al, 2022 36567205 ✓ ✓ ✓ ✓ ✓


« ✓ » 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
IVAnononono
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C0 0.1606 0.12 0.999
VUS1 VUS1 VUS2 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 12
CF 7
CFTR-RD4
  • CBAVD  3
  • Pancreatitis  1
Pending non-CF 1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 4735heterozygoteCFTR-RD-causing - Trans
CFTR-RD-causing - Trans
CFTR-RD-causing - Trans
CBAVD 2747heterozygotevarying clinical consequence- Undef
CBAVD 2264heterozygoteCF-causing- Undef
CF 2620heterozygoteCF-causing- Undef
CF 1541heterozygoteCF-causing- Undef
CF 1540heterozygoteCF-causing- Undef
CF 1310heterozygoteCF-causing- Undef
CF 1309heterozygoteCF-causing- Undef
CF 913heterozygoteCF-causing- Undef
CF 2764heterozygoteCF-causing- Undef
Pending non-CF 4825heterozygoteCFTR-RD-causing - Trans
CFTR-RD-causing - Trans
CFTR-RD-causing - Trans
Pancreatitis 2586heterozygoteCF-causing- Undef


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.