ClinVar Genomic variation as it relates to human health
NM_000132.4(F8):c.3864A>C (p.Ser1288=)
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_000132.4(F8):c.3864A>C (p.Ser1288=)
Variation ID: 41000 Accession: VCV000041000.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154929926 (GRCh38) [ NCBI UCSC ] X: 154158201 (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 May 3, 2013 Feb 20, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000132.4:c.3864A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000123.1:p.Ser1288= synonymous NC_000023.11:g.154929926T>G NC_000023.10:g.154158201T>G NG_011403.2:g.97798A>C LRG_555:g.97798A>C LRG_555t1:c.3864A>C LRG_555p1:p.Ser1288= - Protein change
- Other names
- NM_000132.3(F8):c.3864A>C
- p.Ser1288=
- Canonical SPDI
- NC_000023.11:154929925:T:G
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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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0.16053 (G)
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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 0.08010
The Genome Aggregation Database (gnomAD) 0.09246
Trans-Omics for Precision Medicine (TOPMed) 0.10767
Exome Aggregation Consortium (ExAC) 0.13923
The Genome Aggregation Database (gnomAD), exomes 0.14704
1000 Genomes Project 0.16053
1000 Genomes Project 30x 0.16275
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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F8 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
902 | 1172 |
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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Benign (3) |
reviewed by expert panel
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Feb 1, 2024 | RCV000033893.22 | |
Benign (3) |
criteria provided, single submitter
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- | RCV000243368.9 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Nov 29, 2023 | RCV001705640.5 |
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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Benign
(Feb 01, 2024)
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reviewed by expert panel
Method: curation
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Hereditary factor VIII deficiency disease
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen
Accession: SCV004363661.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
The c.3864A>C (p.Ser1288=) variant is reported at an MAF of 0.3377 (6437/19059 alleles) in the South Asian population in gnomAD v2.1.,1 with 3958 hemizygotes and … (more)
The c.3864A>C (p.Ser1288=) variant is reported at an MAF of 0.3377 (6437/19059 alleles) in the South Asian population in gnomAD v2.1.,1 with 3958 hemizygotes and 424 homozygotes, meeting BA1 criteria of MAF > 0.000333. The synonymous variant is predicted to have no impact on splicing based on SpliceAI score of 0.0, meeting BP4. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8/F9: BA1, BP4. (less)
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Benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary factor VIII deficiency disease
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000482095.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Nov 29, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603520.10
First in ClinVar: Oct 02, 2016 Last updated: Feb 20, 2024 |
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000302442.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Nov 11, 2018)
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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: SCV001833151.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(Aug 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary factor VIII deficiency disease
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001933863.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741641.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929514.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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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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Characterization of F8 defects in haemophilia A in Pakistan: investigation of correlation between mutation type and the in vitro thrombin generation assay. | Khanum F | Haemophilia : the official journal of the World Federation of Hemophilia | 2014 | PMID: 24118398 |
Response to desmopressin in patients with mild hemophilia A caused by the F8 c.1910A>G, p.Asn637Ser mutation. | Mauser-Bunschoten EP | Journal of thrombosis and haemostasis : JTH | 2013 | PMID: 24134483 |
Sequence variation data of F8 and F9 genes in functionally validated control individuals: implications on the molecular diagnosis of hemophilia. | Seo JY | Blood research | 2013 | PMID: 24086941 |
Deep intronic 'mutations' cause hemophilia A: application of next generation sequencing in patients without detectable mutation in F8 cDNA. | Pezeshkpoor B | Journal of thrombosis and haemostasis : JTH | 2013 | PMID: 23809411 |
Detection of new mutations and molecular pathology of mild and moderate haemophilia A patients from southern Brazil. | Rosset C | Haemophilia : the official journal of the World Federation of Hemophilia | 2013 | PMID: 23711237 |
Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations. | Riccardi F | Haemophilia : the official journal of the World Federation of Hemophilia | 2010 | PMID: 20331761 |
Molecular analysis of F8 in Lebanese haemophilia A patients: novel mutations and phenotype-genotype correlation. | Djambas Khayat C | Haemophilia : the official journal of the World Federation of Hemophilia | 2008 | PMID: 18479430 |
Sequencing of the factor 8(F8) coding regions in 10 Turkish hemophilia A patients reveals three novel pathological mutations, and one rediagnosis of von Willebrand's disease type 2N. | Berber E | Haemophilia : the official journal of the World Federation of Hemophilia | 2006 | PMID: 16834740 |
Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch. Haemophilia Centres. | Waseem NH | Thrombosis and haemostasis | 1999 | PMID: 10404764 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/c93cdc62-e0c9-4b88-ac1b-eb3bed663994 | - | - | - | - |
Text-mined citations for rs1800292 ...
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.