19-49894380-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152899.2(IL4I1):c.455T>G(p.Val152Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
IL4I1
NM_152899.2 missense
NM_152899.2 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 2.96
Genes affected
IL4I1 (HGNC:19094): (interleukin 4 induced 1) This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5' UTR with the overlapping NUP62 gene. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL4I1 | NM_152899.2 | c.455T>G | p.Val152Gly | missense_variant | 5/8 | ENST00000391826.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL4I1 | ENST00000391826.7 | c.455T>G | p.Val152Gly | missense_variant | 5/8 | 1 | NM_152899.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251434Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727246
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2021 | The c.521T>G (p.V174G) alteration is located in exon 7 (coding exon 4) of the IL4I1 gene. This alteration results from a T to G substitution at nucleotide position 521, causing the valine (V) at amino acid position 174 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Benign
DEOGEN2
Uncertain
D;.;.;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.;.
REVEL
Uncertain
Sift
Benign
T;T;.;.
Sift4G
Benign
T;T;T;D
Polyphen
D;D;D;.
Vest4
MutPred
Loss of stability (P = 0.0147);.;.;.;
MVP
MPC
1.4
ClinPred
D
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