rs2243290

Variant names:

• chr5-132682477-C-A
• rs2243290
• NM_000589.4:c.361-9C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132682477-C-A
• chr5-132682477-C-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.361-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,546,350 control chromosomes in the GnomAD database, including 40,101 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 0.26 (6585 hom., cov: 32)
  • Exomes 𝑓: 0.18 (33516 hom.)
• Consequence: IL4 NM_000589.4 intron
• Scores: Splicing: ADA: 0.002755
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 68 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4	NM_000589.4	c.361-9C>A		intron_variant	Intron 3 of 3	ENST00000231449.7	NP_000580.1
LOC105379176	NR_134248.1	n.153G>T		non_coding_transcript_exon_variant	Exon 1 of 2
IL4	NM_172348.3	c.313-9C>A		intron_variant	Intron 2 of 2		NP_758858.1
IL4	NM_001354990.2	c.*51-9C>A		intron_variant	Intron 4 of 4		NP_001341919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.361-9C>A		intron_variant	Intron 3 of 3	1	NM_000589.4	ENSP00000231449.2
IL4	ENST00000350025.2	c.313-9C>A		intron_variant	Intron 2 of 2	1		ENSP00000325190.3
IL4	ENST00000622422.1	c.*51-9C>A		intron_variant	Intron 4 of 4	1		ENSP00000480581.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39083 AN: 151906 Hom.: 6582 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.269 AC: 66627 AN: 247594 AF XY: 0.250

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.795

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.181 AC: 252305 AN: 1394326 Hom.: 33516 Cov.: 22 AF XY: 0.178 AC XY: 124257 AN XY: 697388

African (AFR) AF: 0.353 AC: 11307 AN: 32024

American (AMR) AF: 0.417 AC: 18307 AN: 43874

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4832 AN: 25644

East Asian (EAS) AF: 0.739 AC: 29060 AN: 39314

South Asian (SAS) AF: 0.165 AC: 13850 AN: 83700

European-Finnish (FIN) AF: 0.344 AC: 18352 AN: 53290

Middle Eastern (MID) AF: 0.124 AC: 699 AN: 5648

European-Non Finnish (NFE) AF: 0.137 AC: 143922 AN: 1052742

Other (OTH) AF: 0.206 AC: 11976 AN: 58090

GnomAD4 genome AF: 0.257 AC: 39121 AN: 152024 Hom.: 6585 Cov.: 32 AF XY: 0.267 AC XY: 19873 AN XY: 74294

African (AFR) AF: 0.347 AC: 14395 AN: 41432

American (AMR) AF: 0.304 AC: 4645 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4013 AN: 5174

South Asian (SAS) AF: 0.191 AC: 919 AN: 4816

European-Finnish (FIN) AF: 0.360 AC: 3791 AN: 10540

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10152 AN: 67982

Other (OTH) AF: 0.232 AC: 491 AN: 2116

Alfa AF: 0.187 Hom.: 7481

Bravo AF: 0.264

Asia WGS AF: 0.467 AC: 1623 AN: 3478

EpiCase AF: 0.131

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.56
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0028
dbscSNV1_RF	Benign	0.23
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: rs2243290; hg19: chr5-132018169; COSMIC: COSV51503592; COSMIC: COSV51503592;