rs448012
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_182925.5(FLT4):āc.2670C>Gā(p.His890Gln) variant causes a missense change. The variant allele was found at a frequency of 0.628 in 1,609,192 control chromosomes in the GnomAD database, including 319,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.61 ( 28934 hom., cov: 32)
Exomes š: 0.63 ( 290749 hom. )
Consequence
FLT4
NM_182925.5 missense
NM_182925.5 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 3.68
Genes affected
FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=1.3976962E-6).
BP6
Variant 5-180619344-G-C is Benign according to our data. Variant chr5-180619344-G-C is described in ClinVar as [Benign]. Clinvar id is 263039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180619344-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLT4 | NM_182925.5 | c.2670C>G | p.His890Gln | missense_variant | 19/30 | ENST00000261937.11 | NP_891555.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLT4 | ENST00000261937.11 | c.2670C>G | p.His890Gln | missense_variant | 19/30 | 1 | NM_182925.5 | ENSP00000261937.6 |
Frequencies
GnomAD3 genomes AF: 0.612 AC: 92873AN: 151658Hom.: 28920 Cov.: 32
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GnomAD3 exomes AF: 0.630 AC: 153516AN: 243662Hom.: 49194 AF XY: 0.623 AC XY: 82868AN XY: 133036
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GnomAD4 exome AF: 0.630 AC: 917892AN: 1457416Hom.: 290749 Cov.: 42 AF XY: 0.627 AC XY: 455002AN XY: 725184
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GnomAD4 genome AF: 0.612 AC: 92924AN: 151776Hom.: 28934 Cov.: 32 AF XY: 0.616 AC XY: 45667AN XY: 74170
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 62% of total chromosomes in ExAC - |
Congenital heart defects, multiple types, 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Hereditary lymphedema type I Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;.;B
Vest4
MutPred
Gain of catalytic residue at H890 (P = 0.0859);Gain of catalytic residue at H890 (P = 0.0859);Gain of catalytic residue at H890 (P = 0.0859);
MPC
ClinPred
T
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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