19-49889729-G-A

Variant names:

• chr19-49889729-G-A
• rs746344996
• NM_152899.2:c.1645C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152899.2(IL4I1):​c.1645C>T​(p.Pro549Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,363,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: IL4I1 NM_152899.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.509
• Publications: 1 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03828323).

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.1645C>T	p.Pro549Ser	missense	Exon 8 of 8	NP_690863.1	Q96RQ9-1
	IL4I1	NM_001258017.2		c.1711C>T	p.Pro571Ser	missense	Exon 10 of 10	NP_001244946.1	Q96RQ9-2
	IL4I1	NM_001258018.2		c.1711C>T	p.Pro571Ser	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.1645C>T	p.Pro549Ser	missense	Exon 8 of 8	ENSP00000375702.1	Q96RQ9-1
	IL4I1	ENST00000341114.7	TSL:1	c.1711C>T	p.Pro571Ser	missense	Exon 10 of 10	ENSP00000342557.2	Q96RQ9-2
	IL4I1	ENST00000595948.5	TSL:1	c.1711C>T	p.Pro571Ser	missense	Exon 10 of 10	ENSP00000472474.1	Q96RQ9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000225 AC: 4 AN: 177556 AF XY: 0.0000214

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: 0.0000464

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000403 AC: 55 AN: 1363276 Hom.: 0 Cov.: 31 AF XY: 0.0000360 AC XY: 24 AN XY: 667088

African (AFR) AF: 0.00 AC: 0 AN: 30168

American (AMR) AF: 0.0000345 AC: 1 AN: 28944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19882

East Asian (EAS) AF: 0.00 AC: 0 AN: 38694

South Asian (SAS) AF: 0.00 AC: 0 AN: 70412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.0000498 AC: 53 AN: 1063984

Other (OTH) AF: 0.0000178 AC: 1 AN: 56056

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000354 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000251 AC: 3

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	0.058
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.016
DANN	Benign	0.62
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.51
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.058
Sift	Benign	0.59	T
Sift4G	Benign	0.68	T
Polyphen		0.0020	B
Vest4		0.047
MutPred		0.25		Loss of catalytic residue at P549 (P = 1e-04)
MVP		0.030
MPC		1.0
ClinPred		0.042	T
GERP RS		-3.8
Varity_R		0.032
gMVP		0.34
Mutation Taster		=96/4	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: rs746344996; hg19: chr19-50392986;