chr13-28015689-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_004119.3(FLT3):c.2554G>A(p.Val852Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,459,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FLT3
NM_004119.3 missense
NM_004119.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 6.14
Genes affected
FLT3 (HGNC:3765): (fms related receptor tyrosine kinase 3) This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2183218).
BP6
?
Variant 13-28015689-C-T is Benign according to our data. Variant chr13-28015689-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2064171.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000178 (26/1459058) while in subpopulation AMR AF= 0.00047 (21/44652). AF 95% confidence interval is 0.000315. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAdExome at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLT3 | NM_004119.3 | c.2554G>A | p.Val852Ile | missense_variant | 21/24 | ENST00000241453.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLT3 | ENST00000241453.12 | c.2554G>A | p.Val852Ile | missense_variant | 21/24 | 1 | NM_004119.3 | P1 | |
FLT3 | ENST00000380987.2 | c.*466G>A | 3_prime_UTR_variant, NMD_transcript_variant | 22/25 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152112Hom.: 0 Cov.: 31 FAILED QC
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GnomAD3 exomes AF: 0.0000837 AC: 21AN: 250836Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135680
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459058Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726100
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GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152112Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74308
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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