ClinVar Genomic variation as it relates to human health
NM_001709.5(BDNF):c.136G>A (p.Val46Met)
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_001709.5(BDNF):c.136G>A (p.Val46Met)
Variation ID: 2636085 Accession: VCV002636085.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p14.1 11: 27658429 (GRCh38) [ NCBI UCSC ] 11: 27679976 (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 Nov 20, 2023 Feb 28, 2024 Jun 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001709.5:c.136G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001700.2:p.Val46Met missense NM_001143805.1:c.136G>A NP_001137277.1:p.Val46Met missense NM_001143806.1:c.136G>A NP_001137278.1:p.Val46Met missense NM_001143807.2:c.136G>A NP_001137279.1:p.Val46Met missense NM_001143808.2:c.136G>A NP_001137280.1:p.Val46Met missense NM_001143809.2:c.223G>A NP_001137281.1:p.Val75Met missense NM_001143810.2:c.382G>A NP_001137282.1:p.Val128Met missense NM_001143811.2:c.136G>A NP_001137283.1:p.Val46Met missense NM_001143812.2:c.136G>A NP_001137284.1:p.Val46Met missense NM_001143813.2:c.136G>A NP_001137285.1:p.Val46Met missense NM_001143814.2:c.136G>A NP_001137286.1:p.Val46Met missense NM_001143816.2:c.136G>A NP_001137288.1:p.Val46Met missense NM_170731.5:c.160G>A NP_733927.1:p.Val54Met missense NM_170732.4:c.136G>A NP_733928.1:p.Val46Met missense NM_170733.4:c.136G>A NP_733929.1:p.Val46Met missense NM_170734.4:c.181G>A NP_733930.1:p.Val61Met missense NM_170735.6:c.136G>A NP_733931.1:p.Val46Met missense NR_002832.2:n.563C>T non-coding transcript variant NR_033312.1:n.494C>T non-coding transcript variant NR_033313.1:n.494C>T non-coding transcript variant NR_033314.1:n.563C>T non-coding transcript variant NR_033315.1:n.494C>T non-coding transcript variant NC_000011.10:g.27658429C>T NC_000011.9:g.27679976C>T NG_011794.1:g.68630G>A NG_011794.2:g.68601G>A - Protein change
- V128M, V46M, V54M, V61M, V75M
- Other names
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- Canonical SPDI
- NC_000011.10:27658428: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
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The frequency of the allele represented by this VCV record.
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- Links
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
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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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BDNF | - | - |
GRCh38 GRCh37 |
7 | 97 | |
BDNF-AS | - | - |
GRCh38 GRCh37 |
- | 92 |
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
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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 (1) |
criteria provided, single submitter
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Jun 27, 2023 | RCV003393061.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 20, 2023 | RCV003778321.1 |
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
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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
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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
(Jun 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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BDNF-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004120150.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The BDNF c.382G>A variant is predicted to result in the amino acid substitution p.Val128Met. This variant can also be referred to as c.136G>A (p.Val46Met) using … (more)
The BDNF c.382G>A variant is predicted to result in the amino acid substitution p.Val128Met. This variant can also be referred to as c.136G>A (p.Val46Met) using an alternative transcript (NM_170735). This variant has been associated with low resilience to psychological stress (referred to as rs146354977 in Azadmarzabadi and Haghighatfard. 2021. PubMed ID: 34492034). This variant is reported in 0.028% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-27679976-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Uncertain significance
(May 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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Invitae
Accession: SCV004678330.1
First in ClinVar: Feb 28, 2024 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with childhood obesity (PMID: 23325614). This variant is present in population databases (rs146354977, gnomAD 0.03%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 46 of the BDNF protein (p.Val46Met). (less)
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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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Screening for genetic variants in BDNF that contribute to childhood obesity. | Zegers D | Pediatric obesity | 2014 | PMID: 23325614 |
Text-mined citations for this variant ...
HelpRecord last updated Mar 11, 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.