Variant NM_000492.4:c.4046G>A


Variant details:
Name NM_000492.4:c.4046G>A
Protein name NP_000483.3:p.(Gly1349Asp)
Genomic name (hg19) chr7:g.117304824G>A    UCSC    gnomAD
#Exon/intron exon 25
Legacy Name G1349D
Class disease-causing
Subclass CF-causing
WT sequence GATGGGGGCTGTGTCCTAAGCCATG G CCACAAGCAGTTGATGTGCTTGGCT
Mutant sequence GATGGGGGCTGTGTCCTAAGCCATG A CCACAAGCAGTTGATGTGCTTGGCT


External sources:
dbSNP
rs193922525


Functional studies:


Reference PMID Splicing mRNA level Maturation Localization Channel fonction (Cl-) Bicarbonate
Anderson and Welsh, 1992 1382316 ✓
Gregory et al, 1991 1712898 ✓ ✓
Mickle et al, 2000 10762539 ✓ ✓
Yu et al, 2012 22293084 ✓ ✓ ✓


« ✓ » 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 yes yesno yes
TEZ-IVA yesnoyesno
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C65 1e-05 0 1
VUS5 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 2
CF 1
CFTR-RD1
  • CBAVD  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 340heterozygoteVUS1 - Cis
CF-causing - Trans
CBAVD 403heterozygoteVUS1 - Cis
CFTR-RD-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.