rs113054726
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001754.5(RUNX1):c.967+8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Consequence
NM_001754.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.967+8A>T | splice_region_variant, intron_variant | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.967+8A>T | splice_region_variant, intron_variant | NM_001754.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251474Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135906
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727222
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74366
ClinVar
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | Nov 13, 2023 | NM_001754.5(RUNX1):c.967+8A>T is an intronic variant. MAF of 0.00048 (0.048%, 12/24970 alleles) in the African subpopulation of the gnomAD V2 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). REVEL score not applicable and SpliceAI ∆ scores <= 0.20 (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.997, <2) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BP4, BP7. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at