NM_000128.4(F11):c.1716+1G>A AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 13, 2023
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:: RCV001383739.5

Allele description [Variation Report for NM_000128.4(F11):c.1716+1G>A]

NM_000128.4(F11):c.1716+1G>A

Genes:

F11-AS1:F11 antisense RNA 1 [Gene - HGNC]
F11:coagulation factor XI [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.2

Genomic location:

Preferred name:

NM_000128.4(F11):c.1716+1G>A

Other names:

F11, IVS14DS, G-A, +1

HGVS:

NC_000004.12:g.186287824G>A
NG_008051.1:g.26861G>A
NM_000128.4:c.1716+1G>AMANE SELECT
LRG_583t1:c.1716+1G>A
LRG_583:g.26861G>A
NC_000004.11:g.187208978G>A
NM_000128.3:c.1716+1G>A
NM_000128.4:c.1716+1G>A

Note:

NCBI staff reviewed the sequence information reported in PubMed 2813350 Fig. 1B to determine the location of this allele on the current reference sequence.

Nucleotide change:

IVS14DS, G-A, +1

Links:

OMIM: 264900.0001; dbSNP: rs373297713

NCBI 1000 Genomes Browser:

rs373297713

Molecular consequence:

NM_000128.4:c.1716+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001582993	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 13, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 2813350, 16835901, 23332144, 17576681, 9536098, 15749683, 27067486, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582993

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 13, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Citations

PubMed

Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations.

Asakai R, Chung DW, Ratnoff OD, Davie EW.

Proc Natl Acad Sci U S A. 1989 Oct;86(20):7667-71.

PubMed [citation]

PMID:: 2813350
PMCID:: PMC298131

Spectrum of factor XI (F11) mutations in the UK population--116 index cases and 140 mutations.

Mitchell M, Mountford R, Butler R, Alhaq A, Dai L, Savidge G, Bolton-Maggs PH.

Hum Mutat. 2006 Aug;27(8):829.

PubMed [citation]

PMID:: 16835901

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001582993.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change affects a donor splice site in intron 14 of the F11 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs373297713, gnomAD 0.04%). Disruption of this splice site has been observed in individual(s) with Factor XI deficiency (PMID: 2813350, 16835901, 23332144). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11890). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the F11 protein in which other variant(s) (p.Thr593Met) have been observed in individuals with F11-related conditions (PMID: 15749683, 27067486). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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