NM_152899.2:c.1489G>A

Variant names:

• chr19-49889885-C-T
• NM_152899.2:c.1489G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_152899.2(IL4I1):​c.1489G>A​(p.Ala497Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL4I1 NM_152899.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4I1	NM_152899.2	MANE Select	c.1489G>A	p.Ala497Thr	missense	Exon 8 of 8	NP_690863.1	Q96RQ9-1
	IL4I1	NM_001258017.2		c.1555G>A	p.Ala519Thr	missense	Exon 10 of 10	NP_001244946.1	Q96RQ9-2
	IL4I1	NM_001258018.2		c.1555G>A	p.Ala519Thr	missense	Exon 10 of 10	NP_001244947.1	Q96RQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4I1	ENST00000391826.7	TSL:1 MANE Select	c.1489G>A	p.Ala497Thr	missense	Exon 8 of 8	ENSP00000375702.1	Q96RQ9-1
	IL4I1	ENST00000341114.7	TSL:1	c.1555G>A	p.Ala519Thr	missense	Exon 10 of 10	ENSP00000342557.2	Q96RQ9-2
	IL4I1	ENST00000595948.5	TSL:1	c.1555G>A	p.Ala519Thr	missense	Exon 10 of 10	ENSP00000472474.1	Q96RQ9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.91	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.86		Gain of glycosylation at S496 (P = 0.1087)
MVP		0.74
MPC		2.1
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.93
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr19-50393142;