Updates for c.4333G>A:
2024-10-14 Class updated from VUS3 to unclassified/non-CF
2024-12-09 Variant classified as VUS non-CF 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.4333G>A


Variant details:
Name NM_000492.4:c.4333G>A
Protein name NP_000483.3:p.(Asp1445Asn)
Genomic name (hg19)     chr7:g.117307052G>A    UCSC    
Genomic name (hg38) chr7:g.117666998G>A    UCSC
#Exon/intron exon 27
Legacy Name D1445N
Class VUS
Subclass non-CF
WT sequence CTTCCGGCAAGCCATCAGCCCCTCC G ACAGGGTGAAGCTCTTTCCCCACCG
Mutant sequence CTTCCGGCAAGCCATCAGCCCCTCC A ACAGGGTGAAGCTCTTTCCCCACCG

Other databases:
dbSNP
no rs



Pathogenicity predictors:



Response to modulators:         +


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

clinical and functional data presented above are provided by Vertex


No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 5
CFTR-RD5
  • Bronchiectasis  1
  • CBAVD  1
  • CRS-NP  1
  • Other  1
  • Pancreatitis  1




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

Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
Pancreatitis 5070heterozygoteCFTR-RD-causing- Undef
Bronchiectasis 5466heterozygoteCF-causing- Undef
CRS-NP 5338heterozygoteCFTR-RD-causing- Undef
Other 5616heterozygoteCFTR-RD-causing - Trans
CBAVD 5063heterozygoteCF-causing- Undef


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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