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NM_000132.4(F8):c.1443+5G>A AND Hereditary factor VIII deficiency disease

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 6, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001002370.9

Allele description [Variation Report for NM_000132.4(F8):c.1443+5G>A]

NM_000132.4(F8):c.1443+5G>A

Gene:
F8:coagulation factor VIII [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000132.4(F8):c.1443+5G>A
HGVS:
  • NC_000023.11:g.154965965C>T
  • NG_011403.2:g.61759G>A
  • NM_000132.4:c.1443+5G>AMANE SELECT
  • LRG_555t1:c.1443+5G>A
  • LRG_555:g.61759G>A
  • NC_000023.10:g.154194240C>T
  • NG_011403.1:g.61759G>A
Links:
dbSNP: rs1195283929
NCBI 1000 Genomes Browser:
rs1195283929
Molecular consequence:
  • NM_000132.4:c.1443+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Hereditary factor VIII deficiency disease (HEMA)
Synonyms:
AUTOSOMAL HEMOPHILIA A; Hemophilia A; Hemophilia A, congenital; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010602; MedGen: C0019069; Orphanet: 98878; OMIM: 134500; OMIM: 306700

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001160278ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)		Likely pathogenic
(Apr 6, 2021) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001160278.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The F8 c.1443+5G>A variant (rs1195283929) is reported in the literature in individuals affected with hemophilia A (Li 2019, Ravanbod 2012). Functional assays indicated one individual had undetectable F8 activity, suggestive of severe disease (Ravanbod 2012). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a moderately conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. In vitro assays on patient DNA demonstrate alternate splicing causing a frameshift (Li 2019). Based on available information, this variant is considered to be likely pathogenic. References: Li D et al. F8 IVS9+5G>A mutation causes moderate haemophilia A. Haemophilia. 2019 Mar;25(2):e132-e135. PMID: 30748051. Ravanbod S et al. Identification of 123 previously unreported mutations in the F8 gene of Iranian patients with haemophilia A. Haemophilia. 2012 May;18(3):e340-6. PMID: 22117735.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024