NM_152899.2:c.1309G>C

Variant names:

• chr19-49890065-C-G
• rs1434139379
• NM_152899.2:c.1309G>C

Variant summary

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

The NM_152899.2(IL4I1):​c.1309G>C​(p.Gly437Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: IL4I1 NM_152899.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• 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.1309G>C	p.Gly437Arg	missense	Exon 8 of 8	NP_690863.1	Q96RQ9-1
	IL4I1	NM_001258017.2		c.1375G>C	p.Gly459Arg	missense	Exon 10 of 10	NP_001244946.1	Q96RQ9-2
	IL4I1	NM_001258018.2		c.1375G>C	p.Gly459Arg	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.1309G>C	p.Gly437Arg	missense	Exon 8 of 8	ENSP00000375702.1	Q96RQ9-1
	IL4I1	ENST00000341114.7	TSL:1	c.1375G>C	p.Gly459Arg	missense	Exon 10 of 10	ENSP00000342557.2	Q96RQ9-2
	IL4I1	ENST00000595948.5	TSL:1	c.1375G>C	p.Gly459Arg	missense	Exon 10 of 10	ENSP00000472474.1	Q96RQ9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000670 AC: 1 AN: 149200 AF XY: 0.0000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397012 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689256

African (AFR) AF: 0.00 AC: 0 AN: 31612

American (AMR) AF: 0.00 AC: 0 AN: 35762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35752

South Asian (SAS) AF: 0.00 AC: 0 AN: 79394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079046

Other (OTH) AF: 0.00 AC: 0 AN: 57978

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000469 Hom.: 0

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	Benign	0.19
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	0.10
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.40
Sift	Benign	0.35	T
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.35
MutPred		0.51		Gain of MoRF binding (P = 0.0376)
MVP		0.79
MPC		2.4
ClinPred		0.91	D
GERP RS		3.2
Varity_R		0.26
gMVP		0.98
Mutation Taster		=90/10	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: rs1434139379; hg19: chr19-50393322;