chr8-92014582-T-C
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The ENST00000523629.6(RUNX1T1):āc.465A>Gā(p.Leu155Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,599,748 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0010 ( 0 hom., cov: 32)
Exomes š: 0.0020 ( 3 hom. )
Consequence
RUNX1T1
ENST00000523629.6 synonymous
ENST00000523629.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.349
Genes affected
RUNX1T1 (HGNC:1535): (RUNX1 partner transcriptional co-repressor 1) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 8-92014582-T-C is Benign according to our data. Variant chr8-92014582-T-C is described in ClinVar as [Benign]. Clinvar id is 719616.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.349 with no splicing effect.
BS2
High AC in GnomAd4 at 153 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RUNX1T1 | NM_001198679.3 | c.642A>G | p.Leu214Leu | synonymous_variant | 4/12 | NP_001185608.1 | ||
RUNX1T1 | NM_001395209.1 | c.549A>G | p.Leu183Leu | synonymous_variant | 4/12 | NP_001382138.1 | ||
RUNX1T1 | NM_001198634.2 | c.498A>G | p.Leu166Leu | synonymous_variant | 3/11 | NP_001185563.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RUNX1T1 | ENST00000523629.6 | c.465A>G | p.Leu155Leu | synonymous_variant | 4/12 | 5 | ENSP00000428543.1 |
Frequencies
GnomAD3 genomes AF: 0.00101 AC: 153AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00103 AC: 249AN: 242140Hom.: 0 AF XY: 0.000889 AC XY: 116AN XY: 130416
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GnomAD4 exome AF: 0.00196 AC: 2840AN: 1447454Hom.: 3 Cov.: 31 AF XY: 0.00185 AC XY: 1328AN XY: 718036
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GnomAD4 genome AF: 0.00100 AC: 153AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74466
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
RUNX1T1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
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