rs71645916

chr5-132679908-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000589.4(IL4):c.360+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,593,930 control chromosomes in the GnomAD database, including 13 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 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (12 hom.)
• Consequence: IL4 NM_000589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd at 304 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4	NM_000589.4	c.360+18C>A		intron_variant		ENST00000231449.7
LOC105379176	NR_134248.1	n.385G>T		non_coding_transcript_exon_variant	2/2
IL4	NM_001354990.2	c.*50+18C>A		intron_variant
IL4	NM_172348.3	c.312+18C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4	ENST00000231449.7	c.360+18C>A		intron_variant		1	NM_000589.4	P1
IL4	ENST00000350025.2	c.312+18C>A		intron_variant		1
IL4	ENST00000622422.1	c.*50+18C>A		intron_variant		1
IL4	ENST00000495905.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 304 AN: 152194 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00119 AC: 277 AN: 231842 Hom.: 4 AF XY: 0.00127 AC XY: 161 AN XY: 126574

Gnomad AFR exome AF: 0.00489

Gnomad AMR exome AF: 0.000711

Gnomad ASJ exome AF: 0.000334

Gnomad EAS exome AF: 0.0000572

Gnomad SAS exome AF: 0.00243

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.000727

Gnomad OTH exome AF: 0.000715

GnomAD4 exome AF: 0.000679 AC: 979 AN: 1441618 Hom.: 12 Cov.: 31 AF XY: 0.000730 AC XY: 522 AN XY: 715218

Gnomad4 AFR exome AF: 0.00437

Gnomad4 AMR exome AF: 0.000989

Gnomad4 ASJ exome AF: 0.000237

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00225

Gnomad4 FIN exome AF: 0.00144

Gnomad4 NFE exome AF: 0.000395

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00200 AC: 305 AN: 152312 Hom.: 1 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74482

Gnomad4 AFR AF: 0.00510

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00210

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs71645916; hg19: chr5-132015600;