rs121912500
Variant summary
Our verdict is Likely benign. Variant got -7 ACMG points: 1P and 8B. BS1BS3PP3
This summary comes from the ClinGen Evidence Repository: The NM_001754.4:c.253C>A (p.His85Asn) variant has a MAF of 0.00043 (0.043%, 8/18,768 alleles) in the East Asian subpopulation of the gnomAD cohort that is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This missense variant has a REVEL score >0.75 (0.852) (PP3). Transactivation assays demonstrating normal transactivation (80-115% of wt) and data from secondary assays demonstrate normal DNA binding, CBFβ binding and sub-cellular localization (BS3; PMID:23817177, PMID:10068652). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BS3, PP3. LINK:https://erepo.genome.network/evrepo/ui/classification/CA123975/MONDO:0011071/008
Frequency
Consequence
NM_001754.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.253C>A | p.His85Asn | missense_variant | 4/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.253C>A | p.His85Asn | missense_variant | 4/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247304Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134480
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460604Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9AN XY: 726690
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 28, 2023 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Jul 26, 2019 | The NM_001754.4:c.253C>A (p.His85Asn) variant has a MAF of 0.00043 (0.043%, 8/18,768 alleles) in the East Asian subpopulation of the gnomAD cohort that is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This missense variant has a REVEL score >0.75 (0.852) (PP3). Transactivation assays demonstrating normal transactivation (80-115% of wt) and data from secondary assays demonstrate normal DNA binding, CBF-beta binding and sub-cellular localization (BS3; PMID: 23817177, PMID: 10068652). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BS3, PP3. - |
Leukemia, acute myeloid, m0 subtype Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2002 | - - |
Transient myeloproliferative disorder of Down syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2002 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at