rs2243282

Variant names:

• chr5-132680862-C-A
• rs2243282
• NM_000589.4:c.360+972C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132680862-C-A
• chr5-132680862-C-T

Variant summary

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

The NM_000589.4(IL4):​c.360+972C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,040 control chromosomes in the GnomAD database, including 6,447 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 0.25 (6447 hom., cov: 32)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 21 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4	NM_000589.4	c.360+972C>A		intron_variant	Intron 3 of 3	ENST00000231449.7	NP_000580.1
IL4	NM_172348.3	c.312+972C>A		intron_variant	Intron 2 of 2		NP_758858.1
IL4	NM_001354990.2	c.*50+972C>A		intron_variant	Intron 4 of 4		NP_001341919.1
LOC105379176	NR_134248.1	n.177-746G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.360+972C>A		intron_variant	Intron 3 of 3	1	NM_000589.4	ENSP00000231449.2
IL4	ENST00000350025.2	c.312+972C>A		intron_variant	Intron 2 of 2	1		ENSP00000325190.3
IL4	ENST00000622422.1	c.*50+972C>A		intron_variant	Intron 4 of 4	1		ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38656 AN: 151922 Hom.: 6445 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.254 AC: 38694 AN: 152040 Hom.: 6447 Cov.: 32 AF XY: 0.265 AC XY: 19691 AN XY: 74290

African (AFR) AF: 0.338 AC: 13987 AN: 41436

American (AMR) AF: 0.303 AC: 4631 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3470

East Asian (EAS) AF: 0.774 AC: 4015 AN: 5186

South Asian (SAS) AF: 0.192 AC: 925 AN: 4822

European-Finnish (FIN) AF: 0.359 AC: 3788 AN: 10540

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10144 AN: 67980

Other (OTH) AF: 0.232 AC: 489 AN: 2110

Alfa AF: 0.214 Hom.: 651

Bravo AF: 0.260

Asia WGS AF: 0.468 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.63
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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: rs2243282; hg19: chr5-132016554;