rs754042987
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. BP7PM2_SupportingBP4
This summary comes from the ClinGen Evidence Repository: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This intronic variant has a Splice AI Δ scores < 0.2 (BP4, BP7). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.662) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4, BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA512319027/MONDO:0100083/008
Frequency
Consequence
NM_001754.5 splice_donor_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.97+4T>C | splice_donor_region_variant, intron_variant | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.97+4T>C | splice_donor_region_variant, intron_variant | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.20e-7 AC: 1AN: 1388504Hom.: 0 Cov.: 25 AF XY: 0.00000144 AC XY: 1AN XY: 694908
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Jun 24, 2024 | This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This intronic variant has a Splice AI Δ scores < 0.2 (BP4, BP7). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.662) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2023 | This sequence change falls in intron 3 of the RUNX1 gene. It does not directly change the encoded amino acid sequence of the RUNX1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 532674). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this variant is associated with skipping of exon 3, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at