chr1-43352208-TC-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate
The NM_005373.3(MPL):c.1566-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,080 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
MPL
NM_005373.3 splice_region, intron
NM_005373.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
Genes affected
MPL (HGNC:7217): (MPL proto-oncogene, thrombopoietin receptor) In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP6
Variant 1-43352208-TC-T is Benign according to our data. Variant chr1-43352208-TC-T is described in ClinVar as [Benign]. Clinvar id is 1533654.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPL | ENST00000372470.9 | c.1566-7delC | splice_region_variant, intron_variant | Intron 10 of 11 | 1 | NM_005373.3 | ENSP00000361548.3 | |||
MPL | ENST00000413998.7 | c.1545-7delC | splice_region_variant, intron_variant | Intron 10 of 11 | 1 | ENSP00000414004.3 | ||||
MPL | ENST00000643351.1 | c.222-7delC | splice_region_variant, intron_variant | Intron 2 of 3 | ENSP00000495154.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151894Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249392Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134902
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726012
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 151894Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74184
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Essential thrombocythemia;C1327915:Congenital amegakaryocytic thrombocytopenia Benign:1
Feb 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at