rs376963970
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001754.5(RUNX1):c.882T>C(p.Pro294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,102 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 Likely benign (★★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
RUNX1
NM_001754.5 synonymous
NM_001754.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.138
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 21-34799386-A-G is Benign according to our data. Variant chr21-34799386-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 532676.Status of the report is reviewed_by_expert_panel, 3 stars.
BP7
?
Synonymous conserved (PhyloP=-0.138 with no splicing effect.
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.882T>C | p.Pro294= | synonymous_variant | 8/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.882T>C | p.Pro294= | synonymous_variant | 8/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251482Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135916
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727248
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Jul 07, 2022 | This c.882T>C (p.Pro294=) synonymous variant is located at a non-conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP score = -0.178882 in GRCh38); it is not predicted to have any splicing impact per SpliceAI (BP7+BP4). 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: BP4 and BP7. - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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