5-132681301-T-G

Variant names:

• chr5-132681301-T-G
• rs2243285
• NM_000589.4:c.361-1185T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000589.4(IL4):​c.361-1185T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 151,928 control chromosomes in the GnomAD database, including 58,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58024 hom., cov: 30)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 9 publications found

Genes affected

IL4 (HGNC:6014): (interleukin 4) The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. IL4 is considered an important cytokine for tissue repair, counterbalancing the effects of proinflammatory type 1 cytokines, however, it also promotes allergic airway inflammation. Moreover, IL-4, a type 2 cytokine, mediates and regulates a variety of human host responses such as allergic, anti-parasitic, wound healing, and acute inflammation. This cytokine has been reported to promote resolution of neutrophil-mediated acute lung injury. In an allergic response, IL-4 has an essential role in the production of allergen-specific immunoglobin (Ig) E. This pro-inflammatory cytokine has been observed to be increased in COVID-19 (Coronavirus disease 2019) patients, but is not necessarily associated with severe COVID-19 pathology. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Aug 2020]

LOC105379176 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000589.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	NM_000589.4	MANE Select	c.361-1185T>G		intron	N/A	NP_000580.1
	IL4	NM_172348.3		c.313-1185T>G		intron	N/A	NP_758858.1
	IL4	NM_001354990.2		c.*51-1185T>G		intron	N/A	NP_001341919.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	ENST00000231449.7	TSL:1 MANE Select	c.361-1185T>G		intron	N/A	ENSP00000231449.2
	IL4	ENST00000350025.2	TSL:1	c.313-1185T>G		intron	N/A	ENSP00000325190.3
	IL4	ENST00000622422.1	TSL:1	c.*51-1185T>G		intron	N/A	ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132547 AN: 151810 Hom.: 57990 Cov.: 30

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.870

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.873 AC: 132638 AN: 151928 Hom.: 58024 Cov.: 30 AF XY: 0.872 AC XY: 64759 AN XY: 74264

African (AFR) AF: 0.826 AC: 34110 AN: 41320

American (AMR) AF: 0.868 AC: 13259 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3015 AN: 3470

East Asian (EAS) AF: 0.935 AC: 4828 AN: 5164

South Asian (SAS) AF: 0.838 AC: 4043 AN: 4826

European-Finnish (FIN) AF: 0.902 AC: 9545 AN: 10580

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60924 AN: 67986

Other (OTH) AF: 0.870 AC: 1835 AN: 2108

Alfa AF: 0.881 Hom.: 20646

Bravo AF: 0.868

Asia WGS AF: 0.904 AC: 3144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.42
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2243285; hg19: chr5-132016993;