ClinVar Genomic variation as it relates to human health
NM_003072.5(SMARCA4):c.76G>A (p.Ala26Thr)
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.
Uncertain significance(1); Benign(1); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003072.5(SMARCA4):c.76G>A (p.Ala26Thr)
Variation ID: 135246 Accession: VCV000135246.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 10984227 (GRCh38) [ NCBI UCSC ] 19: 11094903 (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 9, 2014 May 1, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003072.5:c.76G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003063.2:p.Ala26Thr missense NM_001387283.1:c.76G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001374212.1:p.Ala26Thr missense NM_001128844.3:c.76G>A NP_001122316.1:p.Ala26Thr missense NM_001128845.2:c.76G>A NP_001122317.1:p.Ala26Thr missense NM_001128846.2:c.76G>A NP_001122318.1:p.Ala26Thr missense NM_001128847.4:c.76G>A NP_001122319.1:p.Ala26Thr missense NM_001128848.2:c.76G>A NP_001122320.1:p.Ala26Thr missense NM_001128849.3:c.76G>A NP_001122321.1:p.Ala26Thr missense NM_001374457.1:c.76G>A NP_001361386.1:p.Ala26Thr missense NR_164683.1:n.252G>A non-coding transcript variant NC_000019.10:g.10984227G>A NC_000019.9:g.11094903G>A NG_011556.3:g.28296G>A LRG_878:g.28296G>A LRG_878t1:c.76G>A LRG_878p1:p.Ala26Thr - Protein change
- A26T
- Other names
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- Canonical SPDI
- NC_000019.10:10984226:G:A
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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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00093
The Genome Aggregation Database (gnomAD) 0.00116
Trans-Omics for Precision Medicine (TOPMed) 0.00129
The Genome Aggregation Database (gnomAD), exomes 0.00027
Exome Aggregation Consortium (ExAC) 0.00030
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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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SMARCA4 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5565 | 5588 |
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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not provided (1) |
no classification provided
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Sep 19, 2013 | RCV000122060.3 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 8, 2021 | RCV000566087.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 29, 2016 | RCV000766541.3 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000990146.8 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 15, 2021 | RCV001808347.2 | |
Likely benign (1) |
criteria provided, single submitter
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Sep 26, 2019 | RCV003925210.1 |
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
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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Likely benign
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 16
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002057817.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
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Benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Rhabdoid tumor predisposition syndrome 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000286145.10
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
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Likely benign
(Sep 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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SMARCA4-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004738347.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Uncertain significance
(Sep 29, 2016)
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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: SCV000569850.4
First in ClinVar: Jun 09, 2014 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted SMARCA4 c.76G>A at the cDNA level, p.Ala26Thr (A26T) at the protein level, and results in the change of an Alanine to … (more)
This variant is denoted SMARCA4 c.76G>A at the cDNA level, p.Ala26Thr (A26T) at the protein level, and results in the change of an Alanine to a Threonine (GCC>ACC). This variant was identified in 1/236 healthy Hispanic individuals undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of this individual may not be significant. SMARCA4 Ala26Thr was observed with an allele frequency of 0.3% (12/4378) in African Americans in the NHLBI Exome Sequencing Project. Since Alanine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. SMARCA4 Ala26Thr occurs at a position that is conserved in mammals and is located within the region of interaction with SS18L1/CREST (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether SMARCA4 Ala26Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Rhabdoid tumor predisposition syndrome 2
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001140974.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Jan 08, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002535237.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
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Likely benign
(Mar 29, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000663893.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000086271.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs145867502 ...
HelpRecord last updated May 08, 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.