chr21-34788718-T-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001754.5(RUNX1):c.*3417A>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 0.00021 in 233,464 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00027 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 0 hom. )
Consequence
RUNX1
NM_001754.5 3_prime_UTR
NM_001754.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.925
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS2
High AC in GnomAd4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.*3417A>G | 3_prime_UTR_variant | 9/9 | ENST00000675419.1 | NP_001745.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.*3417A>G | 3_prime_UTR_variant | 9/9 | NM_001754.5 | ENSP00000501943 | A1 | |||
RUNX1 | ENST00000300305.7 | c.*3417A>G | 3_prime_UTR_variant | 8/8 | 1 | ENSP00000300305 | A1 | |||
RUNX1 | ENST00000344691.8 | c.*3417A>G | 3_prime_UTR_variant | 6/6 | 1 | ENSP00000340690 | P4 | |||
RUNX1 | ENST00000437180.5 | c.*3417A>G | 3_prime_UTR_variant | 9/9 | 5 | ENSP00000409227 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000270 AC: 41AN: 152126Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.0000985 AC: 8AN: 81220Hom.: 0 Cov.: 0 AF XY: 0.0000535 AC XY: 2AN XY: 37408
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GnomAD4 genome AF: 0.000269 AC: 41AN: 152244Hom.: 1 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74448
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
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