ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.490A>G (p.Thr164Ala)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.490A>G (p.Thr164Ala)
Variation ID: 632754 Accession: VCV000632754.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117534276 (GRCh38) [ NCBI UCSC ] 7: 117174330 (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 Jun 3, 2019 May 1, 2024 Aug 18, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.490A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Thr164Ala missense NC_000007.14:g.117534276A>G NC_000007.13:g.117174330A>G NG_016465.4:g.73493A>G LRG_663:g.73493A>G LRG_663t1:c.490A>G LRG_663p1:p.Thr164Ala - Protein change
- T164A
- Other names
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- Canonical SPDI
- NC_000007.14:117534275:A:G
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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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00005
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
1000 Genomes Project 30x 0.00016
- Links
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
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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 |
3689 | 5008 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jan 15, 2019 | RCV000780137.9 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Aug 18, 2022 | RCV000802964.8 | |
Uncertain significance (2) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001163277.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 4, 2021 | RCV001509312.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 26, 2022 | RCV002477783.1 |
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
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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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Uncertain significance
(Dec 13, 2018)
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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: SCV000917182.1
First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019 |
Comment:
Variant summary: CFTR c.490A>G (p.Thr164Ala) results in a non-conservative amino acid change of the first nucleotide of exon 5, located in the ABC transporter type … (more)
Variant summary: CFTR c.490A>G (p.Thr164Ala) results in a non-conservative amino acid change of the first nucleotide of exon 5, located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 275348 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.490A>G in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Jan 15, 2019)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001160242.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The CFTR c.490A>G; p.Thr164Ala variant (rs200885306), to our knowledge, is not reported in the medical literature but is reported in the Sick Kids CFTR database … (more)
The CFTR c.490A>G; p.Thr164Ala variant (rs200885306), to our knowledge, is not reported in the medical literature but is reported in the Sick Kids CFTR database (see link). This variant is only observed on five alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The threonine at codon 164 is highly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Thr164Ala variant is uncertain at this time. References: Link to Sick Kids CFTR database: http://www.genet.sickkids.on.ca/cftr/Home.html (less)
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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CFTR-Related Disorders
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001325300.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Feb 04, 2021)
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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: SCV001715939.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Number of individuals with the variant: 1
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Uncertain significance
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027356.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Uncertain significance
(Feb 26, 2022)
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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: SCV002790786.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Aug 18, 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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Invitae
Accession: SCV000942815.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 164 of the CFTR protein (p.Thr164Ala). … (more)
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 164 of the CFTR protein (p.Thr164Ala). This variant is present in population databases (rs200885306, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 632754). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Apr 08, 2021)
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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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Ambry Genetics
Accession: SCV002646087.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.490A>G (p.T164A) alteration is located in exon 5 (coding exon 5) of the CFTR gene. This alteration results from a A to G substitution … (more)
The c.490A>G (p.T164A) alteration is located in exon 5 (coding exon 5) of the CFTR gene. This alteration results from a A to G substitution at nucleotide position 490, causing the threonine (T) at amino acid position 164 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Sep 17, 2018)
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no assertion criteria provided
Method: clinical testing
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CFTR-related disorders
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002080152.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 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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Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations. | Ramalho AS | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2016 | PMID: 25735457 |
Text-mined citations for rs200885306 ...
HelpRecord last updated May 01, 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.