rs11702841
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BA1BP4BP2
This summary comes from the ClinGen Evidence Repository: The NM_001754.4:c.614-34C>T variant has a MAF of 1 (100%) in gnomAD cohort that is ≥ 0.0015 (0.15%) (BA1). This variant is detected in homozygous state in gnomAD population database (BP2). This intronic 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). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10014405/MONDO:0011071/008
Frequency
Genomes: 𝑓 1.0 ( 75579 hom., cov: 26)
Exomes 𝑓: 1.0 ( 487552 hom. )
Consequence
RUNX1
NM_001754.5 intron
NM_001754.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.07
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 -10 ACMG points.
BP2
For more information check the summary or visit ClinGen Evidence Repository.
BP4
For more information check the summary or visit ClinGen Evidence Repository.
BA1
For more information check the summary or visit ClinGen Evidence Repository.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RUNX1 | NM_001754.5 | c.614-34C>T | intron_variant | ENST00000675419.1 | NP_001745.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RUNX1 | ENST00000675419.1 | c.614-34C>T | intron_variant | NM_001754.5 | ENSP00000501943 | A1 |
Frequencies
GnomAD3 genomes 1.00 AC: 151041AN: 151042Hom.: 75520 Cov.: 26
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GnomAD3 exomes AF: 1.00 AC: 245506AN: 245506Hom.: 122753 AF XY: 1.00 AC XY: 133080AN XY: 133080
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GnomAD4 exome AF: 0.999 AC: 975646AN: 976190Hom.: 487552 Cov.: 13 AF XY: 0.999 AC XY: 503815AN XY: 504068
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GnomAD4 genome 1.00 AC: 151159AN: 151160Hom.: 75579 Cov.: 26 AF XY: 1.00 AC XY: 73814AN XY: 73814
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Benign:2
| Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | - - |
| Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:2
| Benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Jul 26, 2019 | The NM_001754.4:c.614-34C>T variant has a MAF of 1 (100%) in gnomAD cohort that is >/= 0.0015 (0.15%) (BA1). This variant is detected in homozygous state in gnomAD population database (BP2). This intronic 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). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, BP4. - |
| Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not specified Benign:1
| Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 03, 2014 | - - |
Acute myeloid leukemia Benign:1
| Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
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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