5-132673907-C-T

Variant names:

• chr5-132673907-C-T
• rs17772853
• NM_000589.4:c.-144C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000589.4(IL4):​c.-144C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 830,508 control chromosomes in the GnomAD database, including 58 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 0.0046 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (49 hom.)
• Consequence: IL4 NM_000589.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00464 (706/152184) while in subpopulation EAS AF = 0.0228 (118/5182). AF 95% confidence interval is 0.0194. There are 9 homozygotes in GnomAd4. There are 475 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 706 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	NM_000589.4	MANE Select	c.-144C>T		upstream_gene	N/A	NP_000580.1	P05112-1
	IL4	NM_172348.3		c.-144C>T		upstream_gene	N/A	NP_758858.1	Q5FC01
	IL4	NM_001354990.2		c.-144C>T		upstream_gene	N/A	NP_001341919.1	U3LVN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4	ENST00000231449.7	TSL:1 MANE Select	c.-144C>T		upstream_gene	N/A	ENSP00000231449.2	P05112-1
	IL4	ENST00000350025.2	TSL:1	c.-144C>T		upstream_gene	N/A	ENSP00000325190.3	P05112-2
	IL4	ENST00000622422.1	TSL:1	c.-144C>T		upstream_gene	N/A	ENSP00000480581.1	U3LVN1

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 706 AN: 152066 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00425 AC: 2882 AN: 678324 Hom.: 49 AF XY: 0.00398 AC XY: 1390 AN XY: 349290

African (AFR) AF: 0.000179 AC: 3 AN: 16798

American (AMR) AF: 0.0228 AC: 619 AN: 27148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15890

East Asian (EAS) AF: 0.0149 AC: 503 AN: 33736

South Asian (SAS) AF: 0.000655 AC: 33 AN: 50352

European-Finnish (FIN) AF: 0.0364 AC: 1280 AN: 35200

Middle Eastern (MID) AF: 0.000508 AC: 2 AN: 3938

European-Non Finnish (NFE) AF: 0.000609 AC: 281 AN: 461668

Other (OTH) AF: 0.00479 AC: 161 AN: 33594

GnomAD4 genome AF: 0.00464 AC: 706 AN: 152184 Hom.: 9 Cov.: 32 AF XY: 0.00638 AC XY: 475 AN XY: 74400

African (AFR) AF: 0.000145 AC: 6 AN: 41520

American (AMR) AF: 0.00857 AC: 131 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0228 AC: 118 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4812

European-Finnish (FIN) AF: 0.0348 AC: 368 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68004

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00243 Hom.: 12

Bravo AF: 0.00326

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		-0.67
PromoterAI		-0.00050	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17772853; hg19: chr5-132009599; COSMIC: COSV107223509;