chr5-132679863-C-T

Position:

• chr5-132679863-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000589.4(IL4):​c.333C>T​(p.Asp111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,613,550 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (67 hom.)
• Consequence: IL4 NM_000589.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.292

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-132679863-C-T is Benign according to our data. Variant chr5-132679863-C-T is described in ClinVar as [Benign]. Clinvar id is 782744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.292 with no splicing effect.
• BS2: High AC in GnomAd4 at 932 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL4	NM_000589.4	c.333C>T	p.Asp111=	synonymous_variant	3/4	ENST00000231449.7
LOC105379176	NR_134248.1	n.430G>A		non_coding_transcript_exon_variant	2/2
IL4	NM_172348.3	c.285C>T	p.Asp95=	synonymous_variant	2/3
IL4	NM_001354990.2	c.*23C>T		3_prime_UTR_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL4	ENST00000231449.7	c.333C>T	p.Asp111=	synonymous_variant	3/4	1	NM_000589.4	P1
IL4	ENST00000350025.2	c.285C>T	p.Asp95=	synonymous_variant	2/3	1
IL4	ENST00000622422.1	c.*23C>T		3_prime_UTR_variant	4/5	1
IL4	ENST00000495905.1	n.299C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 930 AN: 152220 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00923

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00688 AC: 1717 AN: 249456 Hom.: 15 AF XY: 0.00760 AC XY: 1028 AN XY: 135238

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00479

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0126

Gnomad FIN exome AF: 0.00273

Gnomad NFE exome AF: 0.00925

Gnomad OTH exome AF: 0.00721

GnomAD4 exome AF: 0.00767 AC: 11205 AN: 1461212 Hom.: 67 Cov.: 31 AF XY: 0.00791 AC XY: 5748 AN XY: 726928

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00363

Gnomad4 ASJ exome AF: 0.00448

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.00345

Gnomad4 NFE exome AF: 0.00804

Gnomad4 OTH exome AF: 0.00794

GnomAD4 genome AF: 0.00612 AC: 932 AN: 152338 Hom.: 5 Cov.: 32 AF XY: 0.00588 AC XY: 438 AN XY: 74488

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00923

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00679 Hom.: 2

Bravo AF: 0.00522

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.00949

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.54

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: rs35648164; hg19: chr5-132015555; COSMIC: COSV51502807;