rs773671764
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_StrongBS2
The NM_001754.5(RUNX1):c.1044C>T(p.His348=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000056 in 1,606,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
RUNX1
NM_001754.5 synonymous
NM_001754.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.66
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 Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 21-34792534-G-A is Benign according to our data. Variant chr21-34792534-G-A is described in ClinVar as [Uncertain_significance]. Clinvar id is 258182.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.1044C>T | p.His348= | synonymous_variant | 9/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.1044C>T | p.His348= | synonymous_variant | 9/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000132 AC: 3AN: 227610Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 123942
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1454426Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 722794
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74314
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Feb 10, 2022 | NM_001754.5(RUNX1):c.1044C>T (p.His348=) is a synonymous variant. Synonymous variant therefore no REVEL score. SpliceAI is ≤0.20 (0.00) meeting BP4. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at