NM_000132.4(F8):c.3864A>C (p.Ser1288=) AND Hereditary factor VIII deficiency disease

Germline classification:: Benign (3 submissions)
Last evaluated:: Feb 1, 2024
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000033893.22

Allele description [Variation Report for NM_000132.4(F8):c.3864A>C (p.Ser1288=)]

NM_000132.4(F8):c.3864A>C (p.Ser1288=)

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.3864A>C (p.Ser1288=)

Other names:

NM_000132.3(F8):c.3864A>C; p.Ser1288=

HGVS:

NC_000023.11:g.154929926T>G
NG_011403.2:g.97798A>C
NM_000132.4:c.3864A>CMANE SELECT
NP_000123.1:p.Ser1288=
NP_000123.1:p.Ser1288=
LRG_555t1:c.3864A>C
LRG_555:g.97798A>C
LRG_555p1:p.Ser1288=
NC_000023.10:g.154158201T>G
NG_011403.1:g.97798A>C
NM_000132.3:c.3864A>C
p.Ser1288Ser

Links:

dbSNP: rs1800292

NCBI 1000 Genomes Browser:

rs1800292

Molecular consequence:

NM_000132.4:c.3864A>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000482095	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 24134483, 20331761, 16834740, 24086941, 10404764, 18479430, 23809411, 24118398, 23711237 Citation Link,
SCV001933863	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Aug 10, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004363661	ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen	reviewed by expert panel (ClinGen CoagFactor ACMG Specifications F8 V1.0.0)	Benign (Feb 1, 2024)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000482095

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link,

SCV001933863

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Aug 10, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004363661

ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen

reviewed by expert panel

(ClinGen CoagFactor ACMG Specifications F8 V1.0.0)

Benign
(Feb 1, 2024)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Response to desmopressin in patients with mild hemophilia A caused by the F8 c.1910A>G, p.Asn637Ser mutation.

Mauser-Bunschoten EP, Fransen van de Putte DE, Ploos van Amstel HK, Spoor M, Schutgens RE.

J Thromb Haemost. 2013 Dec;11(12):2179-81. doi: 10.1111/jth.12430. No abstract available.

PubMed [citation]

PMID:: 24134483

Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations.

Riccardi F, Tagliaferri A, Martorana D, Rivolta GF, Valdrè L, Rodorigo G, Biasoli C, D'Incà M, Serino ML, Macchi S, Vincenzi D, Arbasi M, Pedrazzi P, Volta M, DI Perna C, Ippolito L, Savi M, Neri TM.

Haemophilia. 2010 Sep 1;16(5):791-800. doi: 10.1111/j.1365-2516.2010.02228.x. Epub 2010 Mar 19.

PubMed [citation]

PMID:: 20331761

See all PubMed Citations (10)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000482095.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV001933863.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen, SCV004363661.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 9, 2024

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