Variant NM_000492.4:c.1475C>T


Variant details:
Name NM_000492.4:c.1475C>T
Protein name NP_000483.3:p.(Ser492Phe)
Genomic name (hg19) chr7:g.117199600C>T    UCSC    gnomAD
#Exon/intron exon 11
Legacy Name S492F
Class disease-causing
Subclass CF-causing
WT sequence CACAGTGGAAGAATTTCATTCTGTT C TCAGTTTTCCTGGATTATGCCTGGC
Mutant sequence CACAGTGGAAGAATTTCATTCTGTT T TCAGTTTTCCTGGATTATGCCTGGC


External sources:
dbSNP
rs121909017


Functional studies:


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


« ✓ » 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-IVAnononono
ELX-TEZ-IVA yesnoyesno


clinical and functional data are provided by Vertex


Pathogenicity predictions:
AGVGD MAPP SIFT PPH2
C25 0.00091 0.04 0.993
VUS2 VUS5 VUS5 VUS5

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




No patient found in CFTR-NGS catalogue


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

TOTAL NUMBER OF PATIENTS 7
CF 6
CFTR-RD1
  • CBAVD  1



Detailed genotypes:
Phenotype Patient ID Variant status Additional variants
CBAVD 887heterozygoteCFTR-RD-causing- Undef
CF 5807heterozygoteVUS3- Undef
CF 1193heterozygoteCF-causing - Trans
CF 1623heterozygoteCF-causing- Undef
CF 2596heterozygoteCF-causing- Undef
CF 3487heterozygoteCF-causing- Undef
CF 4083heterozygoteCF-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.