rs1555889947
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBP6_Strong
The NM_001754.5(RUNX1):c.744C>T(p.Asn248=) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Genomes: not found (cov: 31)
Consequence
RUNX1
NM_001754.5 synonymous
NM_001754.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.99
Genes affected
RUNX1 (HGNC:10471): (RUNX family transcription factor 1) Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 21-34834471-G-A is Benign according to our data. Variant chr21-34834471-G-A is described in ClinVar as [Uncertain_significance]. Clinvar id is 532682.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.744C>T | p.Asn248= | synonymous_variant | 7/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.744C>T | p.Asn248= | synonymous_variant | 7/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2Benign:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2017 | - - |
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Apr 10, 2020 | This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created (BP4). However, evolutionary conservation prediction algorithms predict the site as being moderately conserved (PhyloP score: 2.55 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species. It is also absent from population databases (PM2). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and PM2. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at