21-34788691-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP2BS1
This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.*3444A>G is an intronic variant. MAF of 0.001 (0.1%, 18/15,276 alleles) in the Latino/Admixed American subpopulation of the gnomAD v3.1.2 cohort is ≥ 0.00015 (0.015%) (BS1). This variant is reported in 4 homozygotes in gnomAD v2.1.1 (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: BS1 and BP2 LINK:https://erepo.genome.network/evrepo/ui/classification/CA10653547/MONDO:0011071/008
Frequency
Consequence
NM_001754.5 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.*3444A>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.*3444A>G | 3_prime_UTR_variant | 9/9 | NM_001754.5 | ENSP00000501943 | A1 | |||
RUNX1 | ENST00000300305.7 | c.*3444A>G | 3_prime_UTR_variant | 8/8 | 1 | ENSP00000300305 | A1 | |||
RUNX1 | ENST00000344691.8 | c.*3444A>G | 3_prime_UTR_variant | 6/6 | 1 | ENSP00000340690 | P4 | |||
RUNX1 | ENST00000437180.5 | c.*3444A>G | 3_prime_UTR_variant | 9/9 | 5 | ENSP00000409227 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00209 AC: 318AN: 152174Hom.: 4 Cov.: 32
GnomAD4 exome AF: 0.000640 AC: 52AN: 81190Hom.: 0 Cov.: 0 AF XY: 0.000829 AC XY: 31AN XY: 37376
GnomAD4 genome AF: 0.00209 AC: 318AN: 152292Hom.: 4 Cov.: 32 AF XY: 0.00286 AC XY: 213AN XY: 74466
ClinVar
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 08, 2022 | NM_001754.5(RUNX1):c.*3444A>G is an intronic variant. MAF of 0.001 (0.1%, 18/15,276 alleles) in the Latino/Admixed American subpopulation of the gnomAD v3.1.2 cohort is ≥ 0.00015 (0.015%) (BS1). This variant is reported in 4 homozygotes in gnomAD v2.1.1 (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: BS1 and 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at