chr7-117530975-G-A
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 13P and 1B. PM1PM5PP3PP5_Very_StrongBP4
The NM_000492.4(CFTR):c.350G>A(p.Arg117His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,574 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117C) has been classified as Pathogenic.
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 5 hom. )
Consequence
CFTR
NM_000492.4 missense
NM_000492.4 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 9.52
Genes affected
CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PM1
In a topological_domain Extracellular (size 23) in uniprot entity CFTR_HUMAN there are 19 pathogenic changes around while only 0 benign (100%) in NM_000492.4
PM5
Other missense variant is known to change same aminoacid residue: Variant chr7-117530974-C-T is described in Lovd as [Pathogenic].
PP3
Multiple lines of computational evidence support a deleterious effect 8: BayesDel_noAF, Cadd, Dann, Eigen, M_CAP, phyloP100way_vertebrate, PROVEAN, REVEL [when AlphaMissense, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
PP5
Variant 7-117530975-G-A is Pathogenic according to our data. Variant chr7-117530975-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 7109.Status of the report is practice_guideline, 4 stars. Variant chr7-117530975-G-A is described in Lovd as [Pathogenic]. Variant chr7-117530975-G-A is described in Lovd as [Likely_pathogenic]. Variant chr7-117530975-G-A is described in Lovd as [Pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.1833263). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CFTR | NM_000492.4 | c.350G>A | p.Arg117His | missense_variant | Exon 4 of 27 | ENST00000003084.11 | NP_000483.3 |
Ensembl
Frequencies
GnomAD3 genomes 0.00152 AC: 231AN: 152170Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.00220 AC: 3214AN: 1461404Hom.: 5 Cov.: 31 AF XY: 0.00213 AC XY: 1545AN XY: 727012
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:41Other:2
Revision: practice guideline
LINK: link
Submissions by phenotype
Cystic fibrosis Pathogenic:17Other:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2009 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 27, 2023 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Courtagen Diagnostics Laboratory, Courtagen Life Sciences | Apr 23, 2014 | - - |
| Pathogenic, practice guideline | curation | American College of Medical Genetics and Genomics (ACMG) | Mar 03, 2004 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Nov 11, 2024 | Criteria applied: PS3,PM3_STR,PM5_STR,PP3 - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 23, 2019 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2024 | The p.R117H pathogenic mutation (also known as c.350G>A), located in coding exon 4 of the CFTR gene, results from a G to A substitution at nucleotide position 350. The arginine at codon 117 is replaced by histidine, an amino acid with highly similar properties. The penetrance of the p.R117H mutation is modified by the poly-thymidine tract in CFTR intron 9; decreasing length of the poly-thymidine tract correlates with an increased risk for cystic fibrosis phenotype. When p.R117H is on the same chromosome as 5T (in cis) it is a disease causing mutation; when in cis with 7T, the allele acts as a variant of varying clinical consequence (VVCC) (Sosnay PR et al. Nat. Genet. 2013 Oct; 45(10):1160-7; Sosnay PR et al. Pediatr. Clin. North Am. 2016 Aug;63(4):585-98). In a study of 179 individuals who were compound heterozygous for p.R117H and another pathogenic CFTR mutation, 172 had poly-thymidine variant results documented, with the majority being 7T and only five individuals carrying the 5T allele. Clinical data were available for 166 individuals and diagnoses included: isolated CBAVD (83 individuals), CFTR-related disorder with mild or absent pulmonary disease (67 individuals), late-onset marked pulmonary disease (4 individuals), and asymptomatic (12 individuals) (Thauvin-Robinet C et al. J. Med. Genet., 2013 Apr;50:220-7). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Oct 18, 2019 | NM_000492.3(CFTR):c.350G>A(R117H) is classified as pathogenic in the context of cystic fibrosis. Please note that the R117H mutation is associated with a broad spectrum of disease, ranging from clinically asymptomatic to CAVD/non-classic cystic fibrosis. Individuals with R117H should have testing for the poly-T tract (5T) to determine accurate risk. Individuals with R117H and 5T in cis are at highest risk for CF symptoms. In the absence of the 5T haplotype, the R117H mutation is unlikely to produce significant symptoms of cystic fibrosis. The R117H mutation in combination with another disease causing mutation may result in borderline or elevated sweat chloride and mild clinical symptoms of CF, including male infertility. Sources used for classification include PMID 23974870 and 15371902. In summary, classification of NM_000492.3(CFTR):c.350G>A(R117H) is based on the following criteria: high frequency variant with variable penetrance and variable severity dependent on the presence of other variants in the gene. Please note: this variant was assessed in the context of healthy population screening. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Pars Genome Lab | May 18, 2021 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Jul 22, 2018 | - - |
| not provided, no classification provided | literature only | GeneReviews | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Feb 22, 2022 | - - |
| Pathogenic, low penetrance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2025 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 117 of the CFTR protein (p.Arg117His). This variant is present in population databases (rs78655421, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This missense variant (also known as R117H) most often occurs on the same chromosome as either a pathogenic CFTR variant known as c.1210-34TG[12]T[5] (or 5T;TG12 or TG12-5T) or a benign variant known as c.1210-34TG[10]T[7] (or 7T;TG10 or TG10-7T) (PMID: 7506096, 11491164, 34782259). When present on the opposite chromosome (in trans) from a severe pathogenic CFTR variant, R117H with c.1210-34TG[12]T[5] has been associated with varying degrees of CFTR-related disease, congenital absence of the vas deferens (CAVD), or cystic fibrosis (PMID: 7506096, 11491164). When present on the opposite chromosome (in trans) from a severe pathogenic CFTR variant, R117H with c.1210-34TG[10]T[7] has been associated with variable presentation, even within the same family (PMID:18078365, 27364092). This combination has been reported among individuals with no symptoms of CFTR-related disease, with CAVD, or infrequently, cystic fibrosis. (PMID: 7506096, 7692051, 19880712, 21507732, 23378603). There are limited reports of individuals with homozygosity for R117H with c.1210-34TG[10]T[7] having either no symptoms, pancreatitis, or CAVD (PMID: 21507732, internal data). ClinVar contains an entry for this variant (Variation ID: 7109). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CFTR protein function with a positive predictive value of 80%. The experimental evidence for the R117H-T7 is conflicting. In a heterologous model system, this missense change decreased CFTR activity by approximately 20-30% (PMID: 11242048), while in airway epithelium cells taken from two individuals homozygous for R117H-T7, chloride conductance levels were normal (PMID: 21507732). In summary, the effect of this R117H missense variant is influenced by the length of the polythymidine (polyT) tract on the same chromosome. This variant is reported to cause disease, however, as this variant is associated with a lower penetrance than other pathogenic alleles in the CFTR gene, it has been classified as Pathogenic (low penetrance). - |
| Pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | The CFTR c.350G>A (p.Arg117His) variant is included within the American College of Medical Genetics and Genomics (ACMG) recommended carrier screening panel for cystic fibrosis (Grody et al. 2001). There are multiple clinical implications for the p.Arg117His variant that are dependent on the length of the intron 8 polythymidine tract (polyT) region within the CFTR gene. Kiesewetter et al. (1993) and Massie et al. (2001) assessed the influence of the intron-8 polythymidine sequence (IVS8) on the relationship between the genotype and phenotype of individuals with the p.Arg117His variant. They found that when the p.Arg117His variant was found in cis with five thymidines (5T), and in trans to a pathogenic CF variant, the individual was most commonly affected with classic CF. When the p.Arg117His variant was identified in cis with seven thymidines (7T) and in trans to a pathogenic CF variant, male individuals were often affected with congenital absence of the vas deferens (CAVD), and males and females often presented with a milder variation of CF. In the CFTR2 database, the variant was found in 793 CF patients (808 alleles) and was classified as a mutation of varying clinical consequence (Sosnay et al. 2013). The p.Arg117His variant is reported at a frequency of 0.00256 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the collective evidence, the p.Arg117His variant is classified as pathogenic for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | Nov 05, 2018 | - - |
| Likely pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Nov 04, 2014 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 11, 2016 | Variant summary: The variant of interest causes a missense change involving a conserved nucleotide with 5/5 in silico programs predicting a "deleterious" outcome. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 185/120360 (1/650), which does not exceed the predicted maximum expected allele frequency for a pathogenic CFTR variant of 1/100. The variant of interest has been reported in multiple affected individuals via publications and databases that indicate that the variant of interest is a common disease variant with varying severity dependent on additional CFTR variants in cis and trans. Functional studies indicate that the variant of interest impedes wild type function. In addition, multiple reputable clinical laboratories cite the variant with a classification of "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic. - |
not provided Pathogenic:14
| Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2018 | The R117H variant in the CFTR gene has been reported multiple times previously as a common variant in the CFTR gene (Moskowitz et al., 2008). R117H is a class IV variant which results in defective protein conductance but allows for some residual CFTR function (De Boeck et al., 2014). The severity of disease in individuals with one or two R117H pathogenic variants depends on the presence of a variation in the intron 8 poly T tract and the length of the TG tract in cis configuration with the R117H variant (Moskowitz et al., 2008). A longer TG tract in association with a shorter poly T tract has the strongest adverse effect on intron 8 splicing and are associated with more severe disease (Moskowitz et al., 2008). Individuals with a CFTR pathogenic variant in trans with the R117H variant and 5T variant usually develop the lung disease of CF, but individuals with R117H and the 7T variant or the 9T variant have a highly variable phenotype ranging from clinically asymptomatic to congenital absence of the vas deferens (CAVD) and/or non-classic cystic fibrosis (Moskowitz et al., 2008). Given the available information, we interpret R117H as a pathogenic variant. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 11, 2015 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | May 03, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 15, 2017 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The CFTR p.R117H variant has been reported in the literature as a common variant known to be associated with Cystic Fibrosis (CF) and CF-related diseases, however the phenotype may range from asymptomatic to the classical CF phenotype (Thauvin-Robinet_2013_PMID:23378603; De-Nooijer_2011_PMID:21507732; Thauvin-Robinet_2009_PMID:19880712; Ong_2001_PMID:20301428; White_2001_PMID:11746017; Massie_2001_PMID:11491164; Dasouki_1998_PMID:9557894). The severity of the p.R117H variant has been reported to depend on variation of the poly T tract in intron 9 of the CFTR gene. When the p.R117H variant is found in cis with the 5T variant individuals typically display a more severe phenotype, while individuals with the p.R117H variant and the 7T or 9T variants may have a mild or aymptomatic phenotype (Massie_2001_PMID:11491164; Chmiel_1999_PMID:10103316; Kieswetter_1993_PMID:7506096). The variant was identified in dbSNP (ID: rs78655421) and ClinVar (classified as pathogenic by Ambry Genetics, Laboratory for Molecular Medicine and 17 other submitters; as likely pathogenic by Hudson Alpha Institute for Biotechnology; as uncertain significance by Invitae; and as 'drug response' by PharmGKB). The variant was identified in control databases in 406 of 282346 chromosomes (1 homozygous) at a frequency of 0.001438, and was observed at the highest frequency in the European (non-Finnish) population in 323 of 128902 chromosomes (1 homozygous) (freq: 0.002506) (Genome Aggregation Database March 6, 2019, v2.1.1). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. The p.R117 residue is conserved in mammals and more distantly related organisms, and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein. Functional evidence indicates that the p.R117H variant causes gating defects in CFTR function and results in reduced channel conductance, but retains some residual activity (Yu_2016_PMID:26846474). In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 16, 2023 | - - |
| Likely pathogenic, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Mar 30, 2022 | - - |
| Likely pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics Laboratory, Skane University Hospital Lund | May 27, 2022 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 13, 2023 | The CFTR c.350G>A; p.Arg117His (R117H) variant (rs78655421) is reported in gene-specific databases (CFTR2 Database, ABCC7 Database and references therein) and ClinVar (Variation ID: 7109). Functional analyses show that p.Arg117His protein has reduced conductance and a decreased occupancy in the open state (LaRusch 2014, Van Goor 2014, Yu 2016), and this variant is found in the general population at an overall allele frequency of 0.1% (398/276670 alleles, 1 homozygote) in the Genome Aggregation Database. The p.Arg117His variant is associated with two haplotypes of differing phenotypes when identified with a pathogenic variant on the opposite chromosome. When p.Arg117H is on the same chromosome as the 5T variant in IVS 8, this complex variant is considered pathogenic for cystic fibrosis, but in the absence of 5T, p.Arg117His alone is considered mildly pathogenic and associated with CFTR-related disorders, such as an isolated presentation of congenital bilateral absence of the vas deferens or pancreatitis or mild lung disease (Kiesewetter 1993, Raraigh 2022). References: CFTR2 database: http://cftr2.org/ ABCC7 database: http://abcmutations.hegelab.org/mutationDetails?id=4117 Kiesewetter S et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet. 1993 Nov;5(3):274-8. PMID: 7506096. LaRusch J et al. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. PLoS Genet. 2014 Jul 17;10(7):e1004376. PMID: 25033378. Raraigh KS et al. Complete CFTR gene sequencing in 5,058 individuals with cystic fibrosis informs variant-specific treatment. J Cyst Fibros. 2022 May;21(3):463-470. PMID: 34782259. Van Goor F et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 Jan;13(1):29-36. PMID: 23891399. Yu YC et al. On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator. J Physiol. 2016 Jun 15;594(12):3227-44. PMID: 26846474. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 31, 2023 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Mar 05, 2024 | The CFTR c.350G>A (p.Arg117His) variant causes the synthesis of a partially functional CFTR protein and is associated with variable expressivity. When this variant occurs on the same chromosome (in cis) with the 7T or 9T polymorphism in intron 9 and with another CFTR pathogenic variant associated with cystic fibrosis (CF) on the opposite chromosome (in trans), it is associated with a variable phenotype. The variable phenotype ranges from asymptomatic to CFTR-related disorders, such as congenital bilateral absence of the vas deferens (CBAVD) in males. However, if the c.350G>A (p.Arg117His) CFTR pathogenic variant occurs in cis with the 5T polymorphism in intron 9 and with a CF pathogenic variant in trans, it is associated with CF (PMID: 32404922 (2020) and CFTR2 database (https://cftr2.org/)). Genetic counseling and testing of at-risk relatives are recommended. - |
| Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | CFTR: PS3:Very Strong, PP4:Strong - |
Cystic fibrosis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation Pathogenic:2
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 24, 2018 | The p.Arg117His variant in the CFTR gene is an established variant for cystic fi brosis (CF) that is recommended for by the American College of Medical Genetics (ACMG) for inclusion on the CF population carrier screening panel (Watson 2004, Moskowitz 2008, Castellani 2008). Functional studies have shown that the p.Arg11 7His variant results in defective protein conductance but retains some residual CFTR function (De Boek 2014). As a result, this variant has been classified as a class IV variant. The severity of lung disease in individuals that are compound heterozygous or homozygous for p.Arg117His variant is contingent on the presenc e of a variation in the poly T/poly TG tract of intron 8 that is in cis (same ch romosome copy) with p.Arg117His. A shorter poly T tract together with a longer T G tract results in the strongest aberrant impact to intron 8 splicing and theref ore associated with more severe disease (Moskowitz 2008). Therefore, individuals with a pathogenic CF variant on one chromosome copy and a 5T variant in cis wit h the p.Arg117His variant on the other chromosome copy usually develop CF-relate d lung disease. In contrast, those with p.Arg117His variant in cis with 7T or 9T variant have a highly variable phenotype that can range from clinically asympto matic to congenital absence of the vas deferens (CAVD) in males and/or non-class ic CF (Kieswetter 1993, Massie 2001). In summary, this variant is classified as pathogenic for CF and related disorders in an autosomal recessive manner. ACMG/A MP criteria applied: PM3_VeryStrong, PS3_Moderate. - |
CFTR-related disorder Pathogenic:2
| Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 23, 2019 | - - |
Congenital bilateral aplasia of vas deferens from CFTR mutation Pathogenic:2
| Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2009 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Nov 26, 2024 | Criteria applied: PS3,PM3_STR,PM5_STR,PP3; Identified as compound heterozygous with NM_000492.4:c.3794G>A - |
Obstructive azoospermia Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Reproductive Genetics, University of Münster | Aug 23, 2021 | - - |
Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre | Mar 14, 2024 | - - |
Cystic fibrosis;C0238339:Hereditary pancreatitis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation;C2749757:Bronchiectasis with or without elevated sweat chloride 1 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 24, 2024 | - - |
Bronchiectasis with or without elevated sweat chloride 1 Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 30, 2024 | - - |
ivacaftor response - Efficacy Other:1
| drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Efficacy |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;M;.;.;.;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;N;.;.;N;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.;D;.
Sift4G
Pathogenic
D;D;.;.;D;.
Polyphen
1.0
.;D;.;.;.;.
Vest4
0.88
MVP
MPC
0.011
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at