5-132680703-C-T

Position:

• chr5-132680703-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000231449.7(IL4):​c.360+813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.026 (10 hom., cov: 0)
• Consequence: IL4 ENST00000231449.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0264 (45/1706) while in subpopulation AFR AF= 0.0309 (11/356). AF 95% confidence interval is 0.0205. There are 10 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL4	NM_000589.4	c.360+813C>T		intron_variant		ENST00000231449.7	NP_000580.1
LOC105379176	NR_134248.1	n.177-587G>A		intron_variant, non_coding_transcript_variant
IL4	NM_001354990.2	c.*50+813C>T		intron_variant			NP_001341919.1
IL4	NM_172348.3	c.312+813C>T		intron_variant			NP_758858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL4	ENST00000231449.7	c.360+813C>T		intron_variant		1	NM_000589.4	ENSP00000231449	P1
IL4	ENST00000350025.2	c.312+813C>T		intron_variant		1		ENSP00000325190
IL4	ENST00000622422.1	c.*50+813C>T		intron_variant		1		ENSP00000480581

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 44 AN: 1700 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0690

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0264 AC: 45 AN: 1706 Hom.: 10 Cov.: 0 AF XY: 0.0308 AC XY: 26 AN XY: 844

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0690

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.00

Alfa AF: 0.831 Hom.: 872

Bravo AF: 0.901

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.6
DANN	Benign	0.31

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: rs2243281; hg19: chr5-132016395;