19-49891107-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152899.2(IL4I1):c.637G>A(p.Glu213Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000105 in 1,611,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
IL4I1
NM_152899.2 missense, splice_region
NM_152899.2 missense, splice_region
Scores
6
8
5
Splicing: ADA: 0.9975
2
Clinical Significance
Conservation
PhyloP100: 4.93
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.637G>A | p.Glu213Lys | missense_variant, splice_region_variant | 7/8 | ENST00000391826.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL4I1 | ENST00000391826.7 | c.637G>A | p.Glu213Lys | missense_variant, splice_region_variant | 7/8 | 1 | NM_152899.2 | P2 | |
IL4I1 | ENST00000341114.7 | c.703G>A | p.Glu235Lys | missense_variant, splice_region_variant | 9/10 | 1 | A2 | ||
IL4I1 | ENST00000595948.5 | c.703G>A | p.Glu235Lys | missense_variant, splice_region_variant | 9/10 | 1 | A2 | ||
IL4I1 | ENST00000601717.5 | c.*489G>A | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 10/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247186Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134166
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459744Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 726284
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74322
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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 | Dec 02, 2022 | The c.703G>A (p.E235K) alteration is located in exon 9 (coding exon 6) of the IL4I1 gene. This alteration results from a G to A substitution at nucleotide position 703, causing the glutamic acid (E) at amino acid position 235 to be replaced by a lysine (K). 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
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Pathogenic
D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.
REVEL
Uncertain
Sift
Benign
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
P;P;P
Vest4
MVP
MPC
1.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at