13-113105909-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_019616.4(F7):c.64+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,583,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
F7
NM_019616.4 splice_donor_region, intron
NM_019616.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00008416
2
Clinical Significance
Conservation
PhyloP100: -0.542
Genes affected
F7 (HGNC:3544): (coagulation factor VII) This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 13-113105909-C-T is Benign according to our data. Variant chr13-113105909-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113105909-C-T is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F7 | NM_019616.4 | c.64+4C>T | splice_donor_region_variant, intron_variant | ENST00000346342.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F7 | ENST00000346342.8 | c.64+4C>T | splice_donor_region_variant, intron_variant | 1 | NM_019616.4 | P2 | |||
F7 | ENST00000375581.3 | c.64+4C>T | splice_donor_region_variant, intron_variant | 1 | A2 | ||||
F7 | ENST00000541084.5 | c.64+4C>T | splice_donor_region_variant, intron_variant | 2 | |||||
F7 | ENST00000444337.1 | c.64+4C>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00168 AC: 256AN: 151944Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000288 AC: 59AN: 204834Hom.: 0 AF XY: 0.000237 AC XY: 26AN XY: 109536
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GnomAD4 exome AF: 0.000136 AC: 194AN: 1431030Hom.: 1 Cov.: 31 AF XY: 0.000114 AC XY: 81AN XY: 708142
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital factor VII deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | research | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 27, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Congenital factor VII deficiency;C1832662:Myocardial infarction, susceptibility to Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 22, 2021 | - - |
Factor VII deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at