21-34787947-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1
This summary comes from the ClinGen Evidence Repository: This 3' UTR c.*4188G>C variant is located at a non-conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP = -0.665764 in GRCh38). The variant is present in gnomAD at an allele frequency between 0.015% and 0.15% in a general continental population (European, non-Finnish, subpopulation: 0.03528% in v3) with >5 variant alleles and a minimum of 2000 total alleles (BS1) and has not been described in the literature. 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: BS1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10644605/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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.*4188G>C | 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.*4188G>C | 3_prime_UTR_variant | 9/9 | NM_001754.5 | ENSP00000501943 | A1 | |||
RUNX1 | ENST00000300305.7 | c.*4188G>C | 3_prime_UTR_variant | 8/8 | 1 | ENSP00000300305 | A1 | |||
RUNX1 | ENST00000344691.8 | c.*4188G>C | 3_prime_UTR_variant | 6/6 | 1 | ENSP00000340690 | P4 | |||
RUNX1 | ENST00000437180.5 | c.*4188G>C | 3_prime_UTR_variant | 9/9 | 5 | ENSP00000409227 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152196Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000383 AC: 31AN: 81032Hom.: 0 Cov.: 0 AF XY: 0.000402 AC XY: 15AN XY: 37268
GnomAD4 genome AF: 0.000217 AC: 33AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74502
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Uncertain significance, 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, 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. - |
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | May 26, 2021 | This 3' UTR c.*4188G>C variant is located at a non-conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP = -0.665764 in GRCh38). The variant is present in gnomAD at an allele frequency between 0.015% and 0.15% in a general continental population (European, non-Finnish, subpopulation: 0.03528% in v3) with >5 variant alleles and a minimum of 2000 total alleles (BS1) and has not been described in the literature. 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: BS1. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at