rs6086
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000372470.9(MPL):c.210G>A(p.Pro70=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,613,632 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
ENST00000372470.9 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPL | NM_005373.3 | c.210G>A | p.Pro70= | splice_region_variant, synonymous_variant | 2/12 | ENST00000372470.9 | NP_005364.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPL | ENST00000372470.9 | c.210G>A | p.Pro70= | splice_region_variant, synonymous_variant | 2/12 | 1 | NM_005373.3 | ENSP00000361548 | P1 | |
MPL | ENST00000413998.7 | c.189G>A | p.Pro63= | splice_region_variant, synonymous_variant | 2/12 | 1 | ENSP00000414004 | |||
MPL | ENST00000638732.1 | n.210G>A | splice_region_variant, non_coding_transcript_exon_variant | 2/10 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00449 AC: 683AN: 152108Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00104 AC: 261AN: 250482Hom.: 1 AF XY: 0.000760 AC XY: 103AN XY: 135488
GnomAD4 exome AF: 0.000454 AC: 663AN: 1461406Hom.: 4 Cov.: 33 AF XY: 0.000413 AC XY: 300AN XY: 727022
GnomAD4 genome AF: 0.00447 AC: 681AN: 152226Hom.: 6 Cov.: 32 AF XY: 0.00454 AC XY: 338AN XY: 74422
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 21, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital amegakaryocytic thrombocytopenia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Feb 16, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Thrombocythemia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Essential thrombocythemia;C1327915:Congenital amegakaryocytic thrombocytopenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at