rs3136435
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000506.5(F2):c.316+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,612,902 control chromosomes in the GnomAD database, including 8,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.15 ( 2948 hom., cov: 32)
Exomes 𝑓: 0.077 ( 5874 hom. )
Consequence
F2
NM_000506.5 intron
NM_000506.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0760
Genes affected
F2 (HGNC:3535): (coagulation factor II, thrombin) This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 11-46720876-G-A is Benign according to our data. Variant chr11-46720876-G-A is described in ClinVar as [Benign]. Clinvar id is 1290658.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F2 | NM_000506.5 | c.316+36G>A | intron_variant | ENST00000311907.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F2 | ENST00000311907.10 | c.316+36G>A | intron_variant | 1 | NM_000506.5 | P1 | |||
F2 | ENST00000442468.1 | c.286+36G>A | intron_variant | 3 | |||||
F2 | ENST00000530231.5 | c.316+36G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.148 AC: 22541AN: 151996Hom.: 2937 Cov.: 32
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GnomAD3 exomes AF: 0.0842 AC: 21029AN: 249896Hom.: 1593 AF XY: 0.0789 AC XY: 10660AN XY: 135154
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GnomAD4 exome AF: 0.0765 AC: 111787AN: 1460788Hom.: 5874 Cov.: 31 AF XY: 0.0752 AC XY: 54668AN XY: 726662
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GnomAD4 genome ? AF: 0.148 AC: 22582AN: 152114Hom.: 2948 Cov.: 32 AF XY: 0.145 AC XY: 10799AN XY: 74376
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at