rs535532916
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001754.5(RUNX1):c.*44C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,255,064 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.0085 ( 4 hom., cov: 32)
Exomes 𝑓: 0.012 ( 110 hom. )
Consequence
RUNX1
NM_001754.5 3_prime_UTR
NM_001754.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.209
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 21-34792091-G-C is Benign according to our data. Variant chr21-34792091-G-C is described in ClinVar as [Benign]. Clinvar id is 258181.Status of the report is reviewed_by_expert_panel, 3 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00852 (1282/150452) while in subpopulation NFE AF= 0.0131 (885/67410). AF 95% confidence interval is 0.0124. There are 4 homozygotes in gnomad4. There are 613 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1281 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.*44C>G | 3_prime_UTR_variant | 9/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.*44C>G | 3_prime_UTR_variant | 9/9 | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00852 AC: 1281AN: 150344Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.0109 AC: 59AN: 5428Hom.: 0 AF XY: 0.0112 AC XY: 39AN XY: 3478
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GnomAD4 exome AF: 0.0124 AC: 13700AN: 1104612Hom.: 110 Cov.: 17 AF XY: 0.0123 AC XY: 6571AN XY: 536204
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GnomAD4 genome ? AF: 0.00852 AC: 1282AN: 150452Hom.: 4 Cov.: 32 AF XY: 0.00834 AC XY: 613AN XY: 73504
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2018 | - - |
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Jun 30, 2022 | NM_001754.5(RUNX1):c.*44C>G is a 3' UTR variant. MAF of 0.01 (1.31%, 885/67420 alleles) in the European (non-Finnish) subpopulation of the gnomAD v3.1.2 cohort is ≥ 0.0015 (0.15%) (BA1). This variant is reported in 4 homozygotes in gnomAD v3.1.2 (BP2). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2 - |
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at