ClinVar Genomic variation as it relates to human health
NM_001101.5(ACTB):c.586C>T (p.Arg196Cys)
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_001101.5(ACTB):c.586C>T (p.Arg196Cys)
Variation ID: 29600 Accession: VCV000029600.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5528497 (GRCh38) [ NCBI UCSC ] 7: 5568128 (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 Oct 31, 2013 Feb 14, 2024 Aug 23, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001101.5:c.586C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001092.1:p.Arg196Cys missense NC_000007.14:g.5528497G>A NC_000007.13:g.5568128G>A NG_007992.1:g.7105C>T LRG_132:g.7105C>T LRG_132t1:c.586C>T LRG_132p1:p.Arg196Cys P60709:p.Arg196Cys - Protein change
- R196C
- Other names
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- Canonical SPDI
- NC_000007.14:5528496: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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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
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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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ACTB | No evidence available | No evidence available |
GRCh38 GRCh37 |
536 | 585 |
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 (4) |
criteria provided, single submitter
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Aug 23, 2022 | RCV000022440.37 | |
Pathogenic (2) |
criteria provided, single submitter
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Jul 21, 2020 | RCV000059720.3 |
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
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
(Jul 21, 2020)
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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: SCV000617032.2
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 22366783, 32506774, 23756437, 25052316, 24211661, 27625340, 30733661, 11311002) (less)
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Pathogenic
(Aug 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Baraitser-Winter syndrome 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001214546.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 29600). This missense change has been observed in individual(s) with Baraitser-Winter syndrome (PMID: 22366783, 23756437, 25052316). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 196 of the ACTB protein (p.Arg196Cys). (less)
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Pathogenic
(Apr 15, 2014)
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no assertion criteria provided
Method: clinical testing
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Iris coloboma with ptosis, hypertelorism, and mental retardation
Affected status: yes
Allele origin:
germline
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Department of Genetics, Robert DEBRE University Hospital
Accession: SCV000148643.1
First in ClinVar: Aug 25, 2014 Last updated: Aug 25, 2014 |
Number of individuals with the variant: 5
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Pathogenic
(Feb 01, 2014)
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no assertion criteria provided
Method: literature only
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BARAITSER-WINTER SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000043729.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 11, 2018 |
Comment on evidence:
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310), Riviere et al. (2012) identified a heterozygous C-to-T transition at nucleotide 586 of the ACTB gene, resulting … (more)
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310), Riviere et al. (2012) identified a heterozygous C-to-T transition at nucleotide 586 of the ACTB gene, resulting in an arg-to-cys substitution at codon 196 (R196C). This mutation was not found in 214 other exomes. In a patient (patient 3) with a severe BRWS1 phenotype, previously reported by Der Kaloustian et al. (2001), Di Donato et al. (2014) identified a c.586C-T transition (c.586C-T, NM_001101.3) in the ACTB gene, resulting in the R196C mutation. They noted that the patient with the R196C mutation reported by Riviere et al. (2012) had a mild form of the disorder. Di Donato et al. (2014) suggested that the more severe phenotype in their patient may be due to an unknown genetic modifier that has an impact on the clinical severity and malformation spectrum. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Baraitser-Winter syndrome 1
Affected status: yes
Allele origin:
de novo
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2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens
Accession: SCV001794217.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Indication for testing: Multiple structural anomalies in the anatomy scan of 2nd trimester of pregnancy
Sex: male
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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UniProtKB/Swiss-Prot
Accession: SCV000091290.1
First in ClinVar: Oct 31, 2013 Last updated: Oct 31, 2013 |
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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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Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases. | Verloes A | European journal of human genetics : EJHG | 2015 | PMID: 25052316 |
Severe forms of Baraitser-Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations. | Di Donato N | European journal of human genetics : EJHG | 2014 | PMID: 23756437 |
De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. | Rivière JB | Nature genetics | 2012 | PMID: 22366783 |
A new syndrome with craniofacial and skeletal dysmorphisms and developmental delay. | Der Kaloustian VM | Clinical dysmorphology | 2001 | PMID: 11311002 |
Text-mined citations for rs281875333 ...
HelpRecord last updated Feb 14, 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.