ClinVar Genomic variation as it relates to human health
NM_000080.4(CHRNE):c.130dup (p.Glu44fs)
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_000080.4(CHRNE):c.130dup (p.Glu44fs)
Variation ID: 243030 Accession: VCV000243030.51
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 17p13.2 17: 4902679-4902680 (GRCh38) [ NCBI UCSC ] 17: 4805974-4805975 (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 Jul 25, 2016 Feb 20, 2024 Jan 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000080.4:c.130dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000071.1:p.Glu44fs frameshift NM_000080.4:c.130dupG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001145536.2:c.*2149dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_000080.3:c.130dup NC_000017.11:g.4902682dup NC_000017.10:g.4805977dup NG_008029.2:g.5396dup LRG_1254:g.5396dup LRG_1254t1:c.130dup LRG_1254p1:p.Glu44fs - Protein change
- E44fs
- Other names
- p.Glu44GlyfsX3
- Canonical SPDI
- NC_000017.11:4902679:CCC:CCCC
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- protein truncation Variation Ontology [VariO:0015]
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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.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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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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C17orf107 | - | - | - |
GRCh38 GRCh37 |
- | 765 |
CHRNE | - | - |
GRCh38 GRCh37 |
340 | 1314 |
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
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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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Pathogenic (3) |
criteria provided, single submitter
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Sep 17, 2018 | RCV000235039.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 16, 2023 | RCV000487050.12 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2024 | RCV000531169.14 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 11, 2022 | RCV001843011.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 5, 2022 | RCV001813774.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2021 | RCV001814127.2 |
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
(Sep 17, 2018)
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criteria provided, single submitter
Method: clinical testing
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Congenital myasthenic syndrome
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000967660.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Glu44GlyfsX3 variant in CHRNE is a well-established pathogenic variant and has been reported in >20 Spanish and Portuguese individuals with congenital mya sthenic syndrome … (more)
The p.Glu44GlyfsX3 variant in CHRNE is a well-established pathogenic variant and has been reported in >20 Spanish and Portuguese individuals with congenital mya sthenic syndrome (Ohno 1998, Mihaylova 2010, Natera-de Benito 2017, Estephan 201 8). It has been reported as Pathogenic in ClinVar (Variation ID 243030), and has been identified in 0.06% (20/33580) of Latino chromosomes by the Genome Aggrega tion Database (gnomAD, http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consi stent with a recessive carrier frequency. This variant is predicted to cause a f rameshift, which alters the protein?s amino acid sequence beginning at position 44 and leads to a premature termination codon 3 amino acids downstream. This alt eration is then predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for congenital myasth enic syndrome in an autosomal recessive manner. ACMG/AMP Criteria applied: PVS1, PM3_VeryStrong, PS3_Supporting. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Abnormality of the musculature
Affected status: yes
Allele origin:
germline
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Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755187.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Myasthenic syndrome, slow-channel congenital
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002061247.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.130dupG;p.(Glu44Glyfs*3) is a null frameshift variant (NMD) in the CHRNE gene and predicts alteration of the nonsense-mediate decay - NMD is present in a … (more)
The c.130dupG;p.(Glu44Glyfs*3) is a null frameshift variant (NMD) in the CHRNE gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevantexon to the transcript -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 243030; PMID: 20301347; 9708546; 22678886; 29383513;29054425; 20562457; 9708546PS4. The variant is present at low allele frequencies population databases (rs762368691– gnomAD 0.007248%; ABraOM 0.000854 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Glu44Glyfs*3) was detected in trans with a pathogenic variant (PMID: 29383513, 29054425) - PM3. The variant co-segregated with disease in multiple affected family members (PMID: 29383513) - PP1_moderate. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(Aug 04, 2017)
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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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Genetic Services Laboratory, University of Chicago
Accession: SCV002070499.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Pathogenic
(Nov 27, 2021)
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criteria provided, single submitter
Method: clinical testing
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Congenital myasthenic syndrome 4A
Congenital myasthenic syndrome 4B Congenital myasthenic syndrome 4C (Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002102398.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
Comment:
A homozygous single base pair duplication in exon 2 of the CHRNE gene that results in a frameshift and premature truncation of the protein 3 … (more)
A homozygous single base pair duplication in exon 2 of the CHRNE gene that results in a frameshift and premature truncation of the protein 3 amino acids down stream to codon 44 was detected. This variant has not been reported in the 1000 genomes database and has a minor allele frequency of 0.007% in the gnomAD. The observed variation has previously been reported in patients affected with congenital myasthenic syndrome. (less)
Clinical Features:
Dysarthria (present) , Dysphagia (present) , Abnormal thymus morphology (present) , EMG: impaired neuromuscular transmission (present) , Hypotonia (present) , Kyphosis (present) , Difficulty walking … (more)
Dysarthria (present) , Dysphagia (present) , Abnormal thymus morphology (present) , EMG: impaired neuromuscular transmission (present) , Hypotonia (present) , Kyphosis (present) , Difficulty walking (present) (less)
Age: 10-19 years
Sex: male
Ethnicity/Population group: Hindu
Geographic origin: India
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean >80-100X coverage on the Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
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Pathogenic
(Mar 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Congenital myasthenic syndrome 4A
Congenital myasthenic syndrome 4B Congenital myasthenic syndrome 4C
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV002499120.1
First in ClinVar: Apr 16, 2022 Last updated: Apr 16, 2022 |
Comment:
PVS1, PM2, PM3
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Pathogenic
(Aug 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Congenital myasthenic syndrome 4A
Congenital myasthenic syndrome 4C Congenital myasthenic syndrome 4B
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002789684.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Nov 06, 2021)
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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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GeneDx
Accession: SCV000568658.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate impaired a-bgt binding to the acetylcholine receptor (Ohno et al., 1998); Frameshift variant predicted to result in protein truncation or nonsense … (more)
Published functional studies demonstrate impaired a-bgt binding to the acetylcholine receptor (Ohno et al., 1998); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 9708546, 20301347, 29383513, 31773638) (less)
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Pathogenic
(Sep 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Congenital myasthenic syndrome 4A
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004212592.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(May 16, 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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Revvity Omics, Revvity
Accession: SCV002019302.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Congenital myasthenic syndrome 4A
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000641245.10
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu44Glyfs*3) in the CHRNE gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu44Glyfs*3) in the CHRNE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNE are known to be pathogenic (PMID: 22678886). This variant is present in population databases (rs762368691, gnomAD 0.06%). This premature translational stop signal has been observed in individuals with autosomal recessive congenital myasthenic syndrome (PMID: 9708546). This variant is also known as epsilon70insG. ClinVar contains an entry for this variant (Variation ID: 243030). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Congenital myasthenic syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001453140.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Congenital myasthenic syndrome
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000292397.2
First in ClinVar: Jul 25, 2016 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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protein truncation
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Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002102398.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Congenital Myasthenic Syndromes Overview. | Adam MP | - | 2021 | PMID: 20301347 |
A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome. | Estephan EP | Journal of neurology | 2018 | PMID: 29383513 |
Molecular characterization of congenital myasthenic syndromes in Spain. | Natera-de Benito D | Neuromuscular disorders : NMD | 2017 | PMID: 29054425 |
Congenital myasthenic syndromes: achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: a study of 680 patients. | Abicht A | Human mutation | 2012 | PMID: 22678886 |
Molecular characterisation of congenital myasthenic syndromes in Southern Brazil. | Mihaylova V | Journal of neurology, neurosurgery, and psychiatry | 2010 | PMID: 20562457 |
Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor. | Ohno K | Annals of neurology | 1998 | PMID: 9708546 |
Text-mined citations for rs762368691 ...
HelpRecord last updated Mar 17, 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.