chr21-34787995-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001754.5(RUNX1):c.*4140C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 233,288 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0050 ( 2 hom. )
Consequence
RUNX1
NM_001754.5 3_prime_UTR
NM_001754.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0770
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=-0.84).
BP6
?
Variant 21-34787995-G-A is Benign according to our data. Variant chr21-34787995-G-A is described in ClinVar as [Benign]. Clinvar id is 339796.Status of the report is reviewed_by_expert_panel, 3 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00337 (514/152324) while in subpopulation SAS AF= 0.00435 (21/4832). AF 95% confidence interval is 0.00359. There are 2 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 514 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.*4140C>T | 3_prime_UTR_variant | 9/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.*4140C>T | 3_prime_UTR_variant | 9/9 | NM_001754.5 | A1 | |||
RUNX1 | ENST00000300305.7 | c.*4140C>T | 3_prime_UTR_variant | 8/8 | 1 | A1 | |||
RUNX1 | ENST00000344691.8 | c.*4140C>T | 3_prime_UTR_variant | 6/6 | 1 | P4 | |||
RUNX1 | ENST00000437180.5 | c.*4140C>T | 3_prime_UTR_variant | 9/9 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00338 AC: 514AN: 152206Hom.: 2 Cov.: 32
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GnomAD4 exome AF: 0.00497 AC: 402AN: 80964Hom.: 2 Cov.: 0 AF XY: 0.00534 AC XY: 199AN XY: 37240
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | RUNX1: BS1, BS2 - |
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | May 13, 2020 | The c.*4140C>T variant in the 3' UTR has an MAF of 0.005246 (0.5%, 16/3050 alleles) in the South Asian subpopulation of the gnomAD v3 cohort and is >= 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 1 individual in the gnomAD v3 population database (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 12, 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
Calibrated prediction
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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