This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4 of the BCS1L protein (p.Ser4Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BCS1L-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
ClinVar Genomic variation as it relates to human health
NM_001079866.2(BCS1L):c.11C>T (p.Ser4Leu)
Germline
Classification
Help
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.
(2)
Help
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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001079866.2(BCS1L):c.11C>T (p.Ser4Leu)
Variation ID: 2139345 Accession: VCV002139345.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 218660998 (GRCh38) [ NCBI UCSC ] 2: 219525721 (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 Feb 8, 2023 Jul 23, 2024 Oct 9, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001079866.2:c.11C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073335.1:p.Ser4Leu missense NM_001257342.2:c.11C>T NP_001244271.1:p.Ser4Leu missense NM_001257343.2:c.11C>T NP_001244272.1:p.Ser4Leu missense NM_001257344.2:c.11C>T NP_001244273.1:p.Ser4Leu missense NM_001318836.2:c.-40-408C>T intron variant NM_001320717.2:c.11C>T NP_001307646.1:p.Ser4Leu missense NM_001371443.1:c.11C>T NP_001358372.1:p.Ser4Leu missense NM_001371444.1:c.11C>T NP_001358373.1:p.Ser4Leu missense NM_001371446.1:c.11C>T NP_001358375.1:p.Ser4Leu missense NM_001371447.1:c.11C>T NP_001358376.1:p.Ser4Leu missense NM_001371448.1:c.11C>T NP_001358377.1:p.Ser4Leu missense NM_001371449.1:c.11C>T NP_001358378.1:p.Ser4Leu missense NM_001371450.1:c.11C>T NP_001358379.1:p.Ser4Leu missense NM_001371451.1:c.-41+250C>T intron variant NM_001371452.1:c.-41-761C>T intron variant NM_001371453.1:c.-466C>T 5 prime UTR NM_001371454.1:c.-466C>T 5 prime UTR NM_001371455.1:c.-466C>T 5 prime UTR NM_001371456.1:c.-466C>T 5 prime UTR NM_001374085.1:c.11C>T NP_001361014.1:p.Ser4Leu missense NM_001374086.1:c.-466C>T 5 prime UTR NM_004328.5:c.11C>T NP_004319.1:p.Ser4Leu missense NR_163955.1:n.1023C>T non-coding transcript variant NC_000002.12:g.218660998C>T NC_000002.11:g.219525721C>T NG_008018.1:g.6343C>T NG_033099.2:g.3625G>A LRG_539:g.6343C>T LRG_539t1:c.11C>T LRG_539p1:p.Ser4Leu LRG_539t2:c.11C>T LRG_539p2:p.Ser4Leu - Protein change
- S4L
- Other names
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- Canonical SPDI
- NC_000002.12:218660997: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
Help
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
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| 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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| BCS1L | - | - |
GRCh38 GRCh37 |
492 | 530 | |
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. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 9, 2023 | RCV003070802.3 |
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
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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|---|---|---|---|---|---|
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Uncertain significance
(Oct 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003445027.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4 of the BCS1L protein (p.Ser4Leu). … (more)
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4 of the BCS1L protein (p.Ser4Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BCS1L-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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
(Oct 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV005080716.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
|
Comment:
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
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. |
Comment:
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 4 of the BCS1L protein (p.Ser4Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BCS1L-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Citations for germline classification of this variant
Help| There 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 this variant ...
HelpRecord last updated Sep 29, 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.