chr5-132673907-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 706 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4	NM_000589.4	c.-144C>T		upstream_gene_variant		ENST00000231449.7	NP_000580.1
IL4	NM_172348.3	c.-144C>T		upstream_gene_variant			NP_758858.1
IL4	NM_001354990.2	c.-144C>T		upstream_gene_variant			NP_001341919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.-144C>T		upstream_gene_variant		1	NM_000589.4	ENSP00000231449.2
IL4	ENST00000350025.2	c.-144C>T		upstream_gene_variant		1		ENSP00000325190.3
IL4	ENST00000622422.1	c.-144C>T		upstream_gene_variant		1		ENSP00000480581.1

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

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0149

Gnomad4 SAS exome AF: 0.000655

Gnomad4 FIN exome AF: 0.0364

Gnomad4 NFE exome AF: 0.000609

Gnomad4 OTH exome AF: 0.00479

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

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.00106

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00530 Hom.: 7

Bravo AF: 0.00326

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17772853; hg19: chr5-132009599;