Genetic Variant IL4I1:p.Glu465Lys (chr19-49889981-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152899.2(IL4I1):c.1393G>A(p.Glu465Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,570,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

IL4I1
NM_152899.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.249

Publications

3 publications found

Variant links:

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]

IL4I1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028167963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL4I1	NM_152899.2	MANE Select	c.1393G>A	p.Glu465Lys	missense	Exon 8 of 8	NP_690863.1	Q96RQ9-1
IL4I1	NM_001258017.2		c.1459G>A	p.Glu487Lys	missense	Exon 10 of 10	NP_001244946.1	Q96RQ9-2
IL4I1	NM_001258018.2		c.1459G>A	p.Glu487Lys	missense	Exon 10 of 10	NP_001244947.1	Q96RQ9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL4I1	ENST00000391826.7	TSL:1 MANE Select	c.1393G>A	p.Glu465Lys	missense	Exon 8 of 8	ENSP00000375702.1	Q96RQ9-1
IL4I1	ENST00000341114.7	TSL:1	c.1459G>A	p.Glu487Lys	missense	Exon 10 of 10	ENSP00000342557.2	Q96RQ9-2
IL4I1	ENST00000595948.5	TSL:1	c.1459G>A	p.Glu487Lys	missense	Exon 10 of 10	ENSP00000472474.1	Q96RQ9-2

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000396

AC:

AN:

174168

AF XY:

0.000468

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.000225

Gnomad ASJ exome

AF:

0.000805

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000615

Gnomad NFE exome

AF:

0.000719

Gnomad OTH exome

AF:

0.000638

GnomAD4 exome

AF:

0.000457

AC:

648

AN:

1417766

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

310

AN XY:

701754

show subpopulations

African (AFR)

AF:

0.0000621

AC:

AN:

32190

American (AMR)

AF:

0.000131

AC:

AN:

38050

Ashkenazi Jewish (ASJ)

AF:

0.000827

AC:

AN:

25396

East Asian (EAS)

AF:

0.00

AC:

AN:

36758

South Asian (SAS)

AF:

0.00

AC:

AN:

81698

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

49406

Middle Eastern (MID)

AF:

0.000875

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.000541

AC:

590

AN:

1089870

Other (OTH)

AF:

0.000341

AC:

AN:

58684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

100

149

199

249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000368

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68040

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000340

ExAC

AF:

0.000332

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.49

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.6

PhyloP100

-0.25

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.88

REVEL

Benign

0.19

Sift

Benign

0.41

Sift4G

Benign

0.36

Polyphen

0.050

Vest4

0.073

MVP

0.46

MPC

1.2

ClinPred

0.015

GERP RS

-1.3

Varity_R

0.13

gMVP

0.88

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over