chr19-49890562-C-G

Variant names:

• chr19-49890562-C-G
• rs1324488473
• NM_152899.2:c.812G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152899.2(IL4I1):​c.812G>C​(p.Arg271Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.617
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.812G>C	p.Arg271Pro	missense	Exon 8 of 8	NP_690863.1	Q96RQ9-1
	IL4I1	NM_001258017.2		c.878G>C	p.Arg293Pro	missense	Exon 10 of 10	NP_001244946.1	Q96RQ9-2
	IL4I1	NM_001258018.2		c.878G>C	p.Arg293Pro	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.812G>C	p.Arg271Pro	missense	Exon 8 of 8	ENSP00000375702.1	Q96RQ9-1
	IL4I1	ENST00000341114.7	TSL:1	c.878G>C	p.Arg293Pro	missense	Exon 10 of 10	ENSP00000342557.2	Q96RQ9-2
	IL4I1	ENST00000595948.5	TSL:1	c.878G>C	p.Arg293Pro	missense	Exon 10 of 10	ENSP00000472474.1	Q96RQ9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.85	D
Eigen	Benign	0.020
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.62
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.68		Gain of glycosylation at R271 (P = 0.0174)
MVP		0.040
MPC		1.5
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.98
gMVP		0.85
Mutation Taster		=79/21	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

dbSNP: rs1324488473; hg19: chr19-50393819;