21-34834635-G-A
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
Consequence
NM_001754.5 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.614-34C>T | intron_variant | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.614-34C>T | intron_variant | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes AF: 1.00 AC: 151041AN: 151042Hom.: 75520 Cov.: 26
GnomAD3 exomes AF: 1.00 AC: 245506AN: 245506Hom.: 122753 AF XY: 1.00 AC XY: 133080AN XY: 133080
GnomAD4 exome AF: 0.999 AC: 975646AN: 976190Hom.: 487552 Cov.: 13 AF XY: 0.999 AC XY: 503815AN XY: 504068
GnomAD4 genome AF: 1.00 AC: 151159AN: 151160Hom.: 75579 Cov.: 26 AF XY: 1.00 AC XY: 73814AN XY: 73814
ClinVar
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at