ClinVar Genomic variation as it relates to human health
NM_000492.3(CFTR):c.3718-2477C>T
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.3(CFTR):c.3718-2477C>T
Variation ID: 7166 Accession: VCV000007166.138
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117639961 (GRCh38) [ NCBI UCSC ] 7: 117280015 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 29, 2015 Aug 4, 2024 Mar 3, 2004 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3718-2477C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NC_000007.14:g.117639961C>T NC_000007.13:g.117280015C>T NG_016465.4:g.179178C>T NG_062449.1:g.167C>T LRG_663:g.179178C>T LRG_663t1:c.3718-2477C>T - Protein change
- Other names
- 3849+10kbC->T
- 3849+10kbC>T
- 3849+10KB, C-T
- Canonical SPDI
- NC_000007.14:117639960:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00011
Trans-Omics for Precision Medicine (TOPMed) 0.00012
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CFTR | - | - |
GRCh38 GRCh37 |
3806 | 5170 | |
LOC113633877 | - | - | - | GRCh38 | - | 17 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (11) |
practice guideline
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Mar 3, 2004 | RCV000007586.41 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 13, 2017 | RCV000507372.13 | |
Pathogenic (10) |
criteria provided, multiple submitters, no conflicts
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Sep 20, 2023 | RCV000727872.50 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000763159.10 | |
CFTR-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Jan 29, 2018 | RCV001009390.9 |
CFTR-related disorder
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Pathogenic (2) |
criteria provided, single submitter
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Aug 31, 2023 | RCV001826438.11 |
Pathogenic (1) |
criteria provided, single submitter
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Nov 1, 2021 | RCV002257359.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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pathogenic
(Mar 03, 2004)
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practice guideline
Method: curation
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Cystic fibrosis
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
American College of Medical Genetics and Genomics (ACMG)
Study: The ACMG recommended carrier screening panel
Accession: SCV000071406.2 First in ClinVar: Jun 04, 2013 Last updated: Mar 29, 2015 |
Comment:
Converted during submission to Pathogenic.
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Pathogenic
(Mar 17, 2017)
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reviewed by expert panel
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR2
Study: CFTR2
Accession: SCV000071573.4 First in ClinVar: Oct 18, 2013 Last updated: Dec 26, 2017 |
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Pathogenic
(May 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000855365.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Dec 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University
Accession: SCV000891678.1
First in ClinVar: Oct 10, 2018 Last updated: Oct 10, 2018 |
Geographic origin: Middle East
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary pancreatitis
Bronchiectasis with or without elevated sweat chloride 1 Cystic fibrosis Congenital bilateral aplasia of vas deferens from CFTR mutation
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893746.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Sep 05, 2022)
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criteria provided, single submitter
Method: curation
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002573860.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Comment:
This variant was identified in 10 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a … (more)
This variant was identified in 10 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PS3, PM2_SUP, PM3_VSTR, PM4, PP4 (less)
Number of individuals with the variant: 10
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Pathogenic
(Aug 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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CFTR-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004114477.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The CFTR c.3718-2477C>T variant is predicted to interfere with splicing. This variant is also referred to as 3849+10kbC>T or c.3717+12191C>T. This variant has previously been … (more)
The CFTR c.3718-2477C>T variant is predicted to interfere with splicing. This variant is also referred to as 3849+10kbC>T or c.3717+12191C>T. This variant has previously been reported to be causative in multiple cystic fibrosis patients with a mild phenotype (Highsmith et al. 1994. PubMed ID: 7521937; McKone et al. 2003. PubMed ID: 12767731; Duguépéroux et al. 2005. PubMed ID: 15738290; Sosnay et al. 2013. PubMed ID: 23974870; cftr2.org) and is included in the American College Medical Genetics (ACMG) panel of CF variants (Watson et al. 2004. PubMed ID: 15371902; Deignan JL et al. 2023. PubMed ID: 37310422). We classify this variant as pathogenic. (less)
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Pathogenic
(Mar 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002019223.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Sep 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603001.6
First in ClinVar: Sep 30, 2017 Last updated: Feb 20, 2024 |
Comment:
The CFTR c.3718-2477C>T variant (rs75039782), also known as 3717+12191C>T or 3849+10kbC>T, is reported in the literature in individuals affected with pancreatic sufficient cystic fibrosis (Highsmith … (more)
The CFTR c.3718-2477C>T variant (rs75039782), also known as 3717+12191C>T or 3849+10kbC>T, is reported in the literature in individuals affected with pancreatic sufficient cystic fibrosis (Highsmith 1994, McKone 2003, Ooi 2012, Sosnay 2013). This variant is reported in ClinVar (Variation ID: 7166), and is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice site and activating a nearby cryptic acceptor splice site. Functional assays show that this leads to the abnormal inclusion of intronic sequence, in the form of a new 84bp exon in the CFTR mRNA (Highsmith 1994). The new exon also includes an in-frame termination codon, which is predicted to result in a truncated protein and or absent transcript. Based on available information, this variant is considered to be pathogenic. References: Highsmith WE et al. A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N Engl J Med.1994 331(15):974-80. PMID: 7521937 McKone EF et al. Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. Lancet. 2003 361(9370):1671-6. PMID: 12767731 Ooi CY et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012 11(5):355-62. PMID: 22658665 Sosnay PR et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 45(10):1160-7. PMID: 23974870 (less)
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Pathogenic
(Jan 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000074964.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 2024 |
Comment:
This sequence change falls in intron 22 of the CFTR gene. It does not directly change the encoded amino acid sequence of the CFTR protein. … (more)
This sequence change falls in intron 22 of the CFTR gene. It does not directly change the encoded amino acid sequence of the CFTR protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs75039782, gnomAD 0.3%). This variant has been observed in individual(s) with cystic fibrosis (CF) and is included in the American College of Medical Genetics panel of CF variants (PMID: 15371902, 23974870, 26631874). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 3849+10kbC>T in intron 19. ClinVar contains an entry for this variant (Variation ID: 7166). Studies have shown that this variant results in inclusion of a pseudo-exon and introduces a premature termination codon (PMID: 7521937). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848808.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The c.3718-2477C>T variant in CFTR (also known as 3849+10kbC>T) has been reported, in the homozygous and compound heterozygous state, in numerous individuals with cystic fibrosis … (more)
The c.3718-2477C>T variant in CFTR (also known as 3849+10kbC>T) has been reported, in the homozygous and compound heterozygous state, in numerous individuals with cystic fibrosis with and without pancreatic insufficiency (selected publications: Abeliovich 1992 PMID: 1384328, Highsmith 1994 PMID: 7521937, Liang 1998 PMID: 9719631, Watson 2004 PMID: 15371902, de Gracia 2005 PMID: 15994263, Duguépéroux 2005 PMID: 15738290, Ooi 2011 PMID: 20923678). It has also been identified in 0.2% (6/3470) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). This deep intronic variant was classified as Pathogenic on Mar 17 2017 by the ClinGen-approved CFTR2 expert panel (also pathogenic per practice guideline) (Variation ID 7166). In vitro functional studies have shown that this variant creates a cryptic splice site that causes the creation of a new exon containing an in-frame premature stop codon, the resulting mRNA is predicted to undergo nonsense-mediated decay (Highsmith 1994 PMID: 7521937). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive cystic fibrosis. ACMG/AMP Criteria applied: PM2_supporting, PM3_Very Strong, PS3. (less)
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Pathogenic
(Feb 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713434.2
First in ClinVar: Jun 15, 2021 Last updated: Jun 09, 2024 |
Number of individuals with the variant: 10
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Pathogenic
(Mar 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246823.22
First in ClinVar: May 12, 2020 Last updated: Aug 04, 2024 |
Comment:
CFTR: PM3:Very Strong, PM2, PS3:Moderate
Number of individuals with the variant: 3
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Pathogenic
(Dec 13, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917222.2
First in ClinVar: Jun 03, 2019 Last updated: Jun 24, 2023 |
Comment:
Variant summary: The CFTR c.3718-2477C>T variant involves the alteration of a non-conserved deep intronic nucleotide. One in silico tool predicts a disease-causing outcome for this … (more)
Variant summary: The CFTR c.3718-2477C>T variant involves the alteration of a non-conserved deep intronic nucleotide. One in silico tool predicts a disease-causing outcome for this variant. 5/5 splice prediction tools predict a significant impact on splicing. Functional analysis confirms that this variant is associated with an abnormally spliced product (Highsmith_1994). This variant was found in 2/30924 control chromosomes (gnomAD) at a frequency of 0.0000647, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant has been reported in multiple CF patients with a mild phenotype, including 3 homozygotes (Duguproux_2005, Gilbert_1995) and was included in the ACMG CFTR list (Watson_2004). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 29, 2018)
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criteria provided, single submitter
Method: curation
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cystic fibrosis
CFTR-related disorders
Affected status: yes
Allele origin:
germline
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CFTR-France
Accession: SCV001169243.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Comment:
when the variant is in trans with another CF-causing variation, can either result in CF or in a CFTR-RD
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Pathogenic
(Nov 12, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193976.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 06, 2020 |
Comment:
NM_000492.3(CFTR):c.3718-2477C>T(aka 3849+10kbC>T) is classified as pathogenic in the context of cystic fibrosis and is associated with non-classic disease. Sources cited for classification include the following: … (more)
NM_000492.3(CFTR):c.3718-2477C>T(aka 3849+10kbC>T) is classified as pathogenic in the context of cystic fibrosis and is associated with non-classic disease. Sources cited for classification include the following: PMID 23974870. Classification of NM_000492.3(CFTR):c.3718-2477C>T(aka 3849+10kbC>T) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Mar 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: yes
Allele origin:
germline
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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002502265.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(Nov 01, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary pancreatitis
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002529716.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The CFTR c.3718-2477C>T variant has been reported as homozygous and compound heterozygous in numerous individuals with cystic fibrosis (PMID: 1384328, 7521937, 9719631, 15371902, 15994263, 15738290, … (more)
The CFTR c.3718-2477C>T variant has been reported as homozygous and compound heterozygous in numerous individuals with cystic fibrosis (PMID: 1384328, 7521937, 9719631, 15371902, 15994263, 15738290, 20923678). It is also known as 3849+10kb C>T in the literature. The variant has been reported in patients with and without pancreatic insufficiency and to cause a variable phenotype (PMID: 9719631, 15994263, 15738290). Experimental studies have shown that this variant creates a cryptic splice site that causes the creation of a new exon containing an in-frame premature stop codon (PMID: 7521937). It was observed in 18/152004 chromosomes in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID 7166). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Jun 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002568229.1
First in ClinVar: Sep 03, 2022 Last updated: Sep 03, 2022 |
Comment:
PS3, PM2, PM3_Very Strong, PP3
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Pathogenic
(Nov 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Mendelics
Accession: SCV000886228.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(Jul 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV002817249.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
This variant has been reported in affected individuals with Cystic Fibrosis, congenital bilateral absence of the vas deferens, and CFTR related diseases (PMIDs: 23974870 (2013), … (more)
This variant has been reported in affected individuals with Cystic Fibrosis, congenital bilateral absence of the vas deferens, and CFTR related diseases (PMIDs: 23974870 (2013), 24440181 (2014), 28603918 (2017), 28863137 (2017), and 29261177 (2018)). This variant has also been reported to result in aberrant CFTR splicing, specifically the inclusion of an 84-bp pseudo exon containing a premature stop codon (PMIDs: 24440181 (2014) and 28863137 (2017)).This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. (less)
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Pathogenic
(Aug 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134142.4
First in ClinVar: Jan 06, 2020 Last updated: Jan 06, 2024 |
Comment:
This variant has been reported in affected individuals with Cystic Fibrosis, congenital bilateral absence of the vas deferens, and CFTR related diseases (PMIDs: 23974870 (2013), … (more)
This variant has been reported in affected individuals with Cystic Fibrosis, congenital bilateral absence of the vas deferens, and CFTR related diseases (PMIDs: 23974870 (2013), 24440181 (2014), 28603918 (2017), 28863137 (2017), and 29261177 (2018)). This variant has also been reported to result in aberrant CFTR splicing, specifically the inclusion of an 84-bp pseudo exon containing a premature stop codon (PMIDs: 24440181 (2014) and 28863137 (2017)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jul 03, 1993)
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no assertion criteria provided
Method: literature only
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CYSTIC FIBROSIS
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000027787.2
First in ClinVar: Apr 04, 2013 Last updated: Dec 26, 2017 |
Comment on evidence:
Abeliovich et al. (1992) found that among 94 Ashkenazi Jewish patients with cystic fibrosis (CF; 219700) in Israel, 5 mutations accounted for 97% of mutant … (more)
Abeliovich et al. (1992) found that among 94 Ashkenazi Jewish patients with cystic fibrosis (CF; 219700) in Israel, 5 mutations accounted for 97% of mutant CFTR alleles. Four of these were delF508 (602421.0001), G542X (602421.0009), W1282X (602421.0022), and N1303K (602421.0032). The fifth, which accounted for 4% of alleles, was an unusual mutation found by Highsmith (1991). Referred to as 3849+10kbC-T, it was detected by cleavage of a PCR product by HphI. Highsmith et al. (1991) detected the 3849+10kbC-T mutation in a 19-year-old Pakistani woman with mild manifestations of CF and normal sweat chloride values. To explain the milder course of the disease in patients with this mutation, Highsmith et al. (1991) hypothesized that the C-to-T base substitution created an alternative splice site, which resulted in insertion of 84 basepairs into the CFTR coding region. This change may cause synthesis of a protein with normal CFTR function together with a nonfunctional protein. Alternatively, this mutation might lead to production of a protein that is only partly functional and causes milder disease. In Israel, Augarten et al. (1993) investigated 15 patients with CF and this mutation, all Ashkenazi Jews. Their clinical features were compared with those of CF patients with mutations known to be associated with severe disease. Patients with the 3849+10kbC-T mutation were older, had been diagnosed as having CF at a more advanced age, and were in a better nutritional state. Sweat chloride values were normal in 5 of the 15 patients; 4 of these patients and 6 others had normal pancreatic function. However, age-adjusted pulmonary function did not differ between these patients and those with mutations known to cause severe disease. None of the patients with the 3849+10kbC-T mutation had had meconium ileus and none had liver disease or diabetes mellitus. (less)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958004.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744069.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(Jul 26, 2017)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002075873.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Cystic fibrosis
Affected status: unknown
Allele origin:
unknown
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GeneReviews
Accession: SCV001622805.2
First in ClinVar: May 23, 2021 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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The genetic structure of the Turkish population reveals high levels of variation and admixture. | Kars ME | Proceedings of the National Academy of Sciences of the United States of America | 2021 | PMID: 34426522 |
Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients. | Petrova NV | Genes | 2020 | PMID: 32429104 |
Sequencing as a first-line methodology for cystic fibrosis carrier screening. | Beauchamp KA | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 31036917 |
Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests. | Archibald AD | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29261177 |
Cas9/gRNA targeted excision of cystic fibrosis-causing deep-intronic splicing mutations restores normal splicing of CFTR mRNA. | Sanz DJ | PloS one | 2017 | PMID: 28863137 |
CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants. | Claustres M | Human mutation | 2017 | PMID: 28603918 |
Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas. | Brennan ML | The Journal of molecular diagnostics : JMD | 2016 | PMID: 26631874 |
The improvement of the best practice guidelines for preimplantation genetic diagnosis of cystic fibrosis: toward an international consensus. | Girardet A | European journal of human genetics : EJHG | 2016 | PMID: 26014425 |
The relative frequency of CFTR mutation classes in European patients with cystic fibrosis. | De Boeck K | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2014 | PMID: 24440181 |
Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. | Sosnay PR | Nature genetics | 2013 | PMID: 23974870 |
An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. | Lazarin GA | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22975760 |
Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. | Ooi CY | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2012 | PMID: 22658665 |
Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis. | Ooi CY | Gastroenterology | 2011 | PMID: 20923678 |
CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening. | Chávez-Saldaña M | Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion | 2010 | PMID: 21416780 |
Transposable elements in disease-associated cryptic exons. | Vorechovsky I | Human genetics | 2010 | PMID: 19823873 |
Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. | Castellani C | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 18456578 |
Genotype-phenotype correlation for pulmonary function in cystic fibrosis. | de Gracia J | Thorax | 2005 | PMID: 15994263 |
The CFTR 3849+10kbC->T and 2789+5G->A alleles are associated with a mild CF phenotype. | Duguépéroux I | The European respiratory journal | 2005 | PMID: 15738290 |
Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. | Watson MS | Genetics in medicine : official journal of the American College of Medical Genetics | 2004 | PMID: 15371902 |
Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. | McKone EF | Lancet (London, England) | 2003 | PMID: 12767731 |
XV-2c/KM-19 haplotype analysis of cystic fibrosis mutations in Mexican patients. | Orozco L | American journal of medical genetics | 2001 | PMID: 11484207 |
Variable levels of normal RNA in different fetal organs carrying a cystic fibrosis transmembrane conductance regulator splicing mutation. | Chiba-Falek O | American journal of respiratory and critical care medicine | 1999 | PMID: 10351951 |
The molecular basis of disease variability among cystic fibrosis patients carrying the 3849+10 kb C-->T mutation. | Chiba-Falek O | Genomics | 1998 | PMID: 9799593 |
3849 + 10 kb C --> T splicing mutation in Hispanic CF patients. | Liang MH | Molecular genetics and metabolism | 1998 | PMID: 9719631 |
CFTR gene mutations in adults with disseminated bronchiectasis. | Girodon E | European journal of human genetics : EJHG | 1997 | PMID: 9272738 |
Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849 + 10kbC > T: significance for geneticists. | Gilbert F | American journal of medical genetics | 1995 | PMID: 8533846 |
Normal sweat chloride values do not exclude the diagnosis of cystic fibrosis. | Stewart B | American journal of respiratory and critical care medicine | 1995 | PMID: 7533604 |
Independent origins of cystic fibrosis mutations R334W, R347P, R1162X, and 3849 + 10kbC-->T provide evidence of mutation recurrence in the CFTR gene. | Morral N | American journal of human genetics | 1994 | PMID: 7526685 |
A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. | Highsmith WE | The New England journal of medicine | 1994 | PMID: 7521937 |
Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849 + 10 kb C-->T mutation. | Augarten A | Lancet (London, England) | 1993 | PMID: 8100293 |
Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population. | Abeliovich D | American journal of human genetics | 1992 | PMID: 1384328 |
Highsmith, W. E., Burch, L. H., Boat, T. F., Boucher, R. C., Silverman, L. M., Knowles, M. R. Identification of a homozygous point mutation in intron 19 in an inbred CF patient with mild disease and normal sweat chloride: creation of an alternative splice site resulting in base-sequence insertion in CFTR coding region between exons 19 and 20. (Abstract) Pediat. Pulmonol. Suppl. 6: 22A, 1991. | - | - | - | - |
Highsmith, W. E., Jr. Personal Communication. 1991. Chapel Hill, N.C. | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CFTR | - | - | - | - |
https://cftr2.org | - | - | - | - |
https://cftr2.org/ | - | - | - | - |
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Text-mined citations for rs75039782 ...
HelpRecord last updated Aug 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.