rs9332801
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001197104.2(KMT2A):āc.4284A>Cā(p.Ile1428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 1,613,484 control chromosomes in the GnomAD database, including 2,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.042 ( 185 hom., cov: 32)
Exomes š: 0.059 ( 2788 hom. )
Consequence
KMT2A
NM_001197104.2 synonymous
NM_001197104.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.77
Genes affected
KMT2A (HGNC:7132): (lysine methyltransferase 2A) This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 11-118484927-A-C is Benign according to our data. Variant chr11-118484927-A-C is described in ClinVar as [Benign]. Clinvar id is 158702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118484927-A-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.77 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2A | NM_001197104.2 | c.4284A>C | p.Ile1428= | synonymous_variant | 10/36 | ENST00000534358.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2A | ENST00000534358.8 | c.4284A>C | p.Ile1428= | synonymous_variant | 10/36 | 1 | NM_001197104.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0415 AC: 6321AN: 152174Hom.: 185 Cov.: 32
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GnomAD3 exomes AF: 0.0500 AC: 12569AN: 251238Hom.: 401 AF XY: 0.0532 AC XY: 7230AN XY: 135780
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GnomAD4 exome AF: 0.0588 AC: 85866AN: 1461192Hom.: 2788 Cov.: 30 AF XY: 0.0598 AC XY: 43453AN XY: 726904
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GnomAD4 genome ? AF: 0.0415 AC: 6321AN: 152292Hom.: 185 Cov.: 32 AF XY: 0.0426 AC XY: 3169AN XY: 74462
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 19, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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