Updates for c.3476C>T:
2018-03-26 class changed from unclassified to disease-causing
2020-03-26 Subclass changed from undefined to CF-causing




Variant NM_000492.4:c.3476C>T


Variant details:
Name NM_000492.4:c.3476C>T
Protein name NP_000483.3:p.(Ser1159Phe)
Genomic name (hg19)     chr7:g.117267583C>T    UCSC    
Genomic name (hg38) chr7:g.117627529C>T    UCSC
#Exon/intron exon 22
Legacy Name S1159F
Class disease-causing
Subclass CF-causing
WT sequence TTGTTATTTTTATTTCAGATGCGAT C TGTGAGCCGAGTCTTTAAGTTCATT
Mutant sequence TTGTTATTTTTATTTCAGATGCGAT T TGTGAGCCGAGTCTTTAAGTTCATT

Other databases:
dbSNP
rs397508573



Pathogenicity predictors:



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 presented above are provided by Vertex


No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 3
Asymptomatic compound heterozygote 1
CF 2




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

Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CF 4904heterozygoteCF-causing- Undef
CF 4306heterozygoteCF-causing - Trans
Asymptomatic compound heterozygote 4305heterozygotenon-CF - Trans


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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