chr4-55080024-T-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002253.4(KDR):c.3988A>T(p.Ile1330Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,614,160 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 1 hom. )
Consequence
KDR
NM_002253.4 missense
NM_002253.4 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: -0.0160
Genes affected
KDR (HGNC:6307): (kinase insert domain receptor) Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0038380027).
BP6
Variant 4-55080024-T-A is Benign according to our data. Variant chr4-55080024-T-A is described in ClinVar as [Benign]. Clinvar id is 3040151.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 390 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KDR | NM_002253.4 | c.3988A>T | p.Ile1330Leu | missense_variant | 30/30 | ENST00000263923.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KDR | ENST00000263923.5 | c.3988A>T | p.Ile1330Leu | missense_variant | 30/30 | 1 | NM_002253.4 | P1 | |
ENST00000511222.1 | n.233+4782T>A | intron_variant, non_coding_transcript_variant | 5 | ||||||
KDR | ENST00000647068.1 | n.4001A>T | non_coding_transcript_exon_variant | 30/30 |
Frequencies
GnomAD3 genomes AF: 0.00252 AC: 384AN: 152154Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000724 AC: 182AN: 251458Hom.: 0 AF XY: 0.000456 AC XY: 62AN XY: 135896
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GnomAD4 exome AF: 0.000246 AC: 360AN: 1461888Hom.: 1 Cov.: 33 AF XY: 0.000208 AC XY: 151AN XY: 727246
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GnomAD4 genome AF: 0.00256 AC: 390AN: 152272Hom.: 1 Cov.: 33 AF XY: 0.00259 AC XY: 193AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
KDR-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 10, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N
PrimateAI
Benign
T
Polyphen
B;B
Vest4
0.077
MutPred
Loss of methylation at K1328 (P = 0.0522);Loss of methylation at K1328 (P = 0.0522);
MVP
0.068
MPC
0.059
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