11-46719945-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000311907.10(F2):c.240+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,503,966 control chromosomes in the GnomAD database, including 24,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.14 ( 2402 hom., cov: 32)
Exomes 𝑓: 0.16 ( 22069 hom. )
Consequence
F2
ENST00000311907.10 intron
ENST00000311907.10 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.148
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 11-46719945-C-T is Benign according to our data. Variant chr11-46719945-C-T is described in ClinVar as [Benign]. Clinvar id is 1277924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
F2 | NM_000506.5 | c.240+83C>T | intron_variant | ENST00000311907.10 | NP_000497.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
F2 | ENST00000311907.10 | c.240+83C>T | intron_variant | 1 | NM_000506.5 | ENSP00000308541 | P1 | |||
F2 | ENST00000442468.1 | c.210+83C>T | intron_variant | 3 | ENSP00000387413 | |||||
F2 | ENST00000530231.5 | c.240+83C>T | intron_variant | 5 | ENSP00000433907 | |||||
F2 | ENST00000469189.1 | n.363C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.145 AC: 21993AN: 152094Hom.: 2389 Cov.: 32
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GnomAD4 exome AF: 0.158 AC: 214252AN: 1351754Hom.: 22069 Cov.: 25 AF XY: 0.159 AC XY: 106417AN XY: 668400
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GnomAD4 genome AF: 0.145 AC: 22010AN: 152212Hom.: 2402 Cov.: 32 AF XY: 0.154 AC XY: 11463AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at