3-184378790-A-G
Variant names:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001290003.1(THPO):c.-28-413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 984,546 control chromosomes in the GnomAD database, including 122,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.49 ( 18937 hom., cov: 32)
Exomes 𝑓: 0.50 ( 103495 hom. )
Consequence
THPO
NM_001290003.1 intron
NM_001290003.1 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.37
Genes affected
THPO (HGNC:11795): (thrombopoietin) Megakaryocytopoiesis is the cellular development process that leads to platelet production. The main functional protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene. Mutations in this gene are the cause of thrombocythemia 1. Alternative promoter usage and differential splicing result in multiple transcript variants differing in the 5' UTR and/or coding region. Multiple AUG codons upstream of the main open reading frame (ORF) have been identified, and these upstream AUGs inhibit translation of the main ORF at different extent. [provided by RefSeq, Feb 2014]
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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=-0.88).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THPO | NM_001290003.1 | c.-28-413T>C | intron_variant | Intron 1 of 6 | NP_001276932.1 | |||
THPO | NM_001289998.1 | c.-448-413T>C | intron_variant | Intron 1 of 6 | NP_001276927.1 | |||
THPO | NM_001290028.1 | c.-146+801T>C | intron_variant | Intron 1 of 5 | NP_001276957.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
THPO | ENST00000645603.2 | c.-28-413T>C | intron_variant | Intron 2 of 7 | ENSP00000494281.2 | |||||
THPO | ENST00000649095.1 | c.-28-413T>C | intron_variant | Intron 1 of 6 | ENSP00000497904.1 | |||||
ENSG00000289500 | ENST00000691896.2 | n.559A>G | non_coding_transcript_exon_variant | Exon 1 of 1 |
Frequencies
GnomAD3 genomes AF: 0.494 AC: 75118AN: 151918Hom.: 18916 Cov.: 32
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GnomAD4 exome AF: 0.497 AC: 414169AN: 832510Hom.: 103495 Cov.: 29 AF XY: 0.497 AC XY: 190935AN XY: 384464
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GnomAD4 genome AF: 0.495 AC: 75188AN: 152036Hom.: 18937 Cov.: 32 AF XY: 0.489 AC XY: 36330AN XY: 74328
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ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at