rs2234898

Variant names:

• chr16-27362594-G-T
• rs2234898
• NM_000418.4:c.1242G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000418.4(IL4R):​c.1242G>T​(p.Leu414Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,613,786 control chromosomes in the GnomAD database, including 21,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (6757 hom., cov: 32)
  • Exomes 𝑓: 0.12 (14624 hom.)
• Consequence: IL4R NM_000418.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.198
• Publications: 24 publications found

Genes affected

IL4R (HGNC:6015): (interleukin 4 receptor) This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE production. The encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

IL4R Gene-Disease associations (from GenCC):

• IgE responsiveness, atopic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-27362594-G-T is Benign according to our data. Variant chr16-27362594-G-T is described in ClinVar as Benign. ClinVar VariationId is 3056799.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.198 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000418.4. 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
	IL4R	NM_000418.4	MANE Select	c.1242G>T	p.Leu414Leu	synonymous	Exon 11 of 11	NP_000409.1
	IL4R	NM_001257406.2		c.1242G>T	p.Leu414Leu	synonymous	Exon 10 of 10	NP_001244335.1
	IL4R	NM_001257407.2		c.1197G>T	p.Leu399Leu	synonymous	Exon 11 of 11	NP_001244336.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.1242G>T	p.Leu414Leu	synonymous	Exon 11 of 11	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.1242G>T	p.Leu414Leu	synonymous	Exon 10 of 10	ENSP00000441667.2
	IL4R	ENST00000912076.1		c.1263G>T	p.Leu421Leu	synonymous	Exon 10 of 10	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34695 AN: 151934 Hom.: 6733 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.132 AC: 33227 AN: 251330 AF XY: 0.120

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.0556

Gnomad EAS exome AF: 0.0737

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.122 AC: 178610 AN: 1461734 Hom.: 14624 Cov.: 35 AF XY: 0.118 AC XY: 85727 AN XY: 727176

African (AFR) AF: 0.550 AC: 18417 AN: 33470

American (AMR) AF: 0.151 AC: 6742 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0563 AC: 1471 AN: 26136

East Asian (EAS) AF: 0.0685 AC: 2720 AN: 39700

South Asian (SAS) AF: 0.0584 AC: 5038 AN: 86250

European-Finnish (FIN) AF: 0.106 AC: 5671 AN: 53412

Middle Eastern (MID) AF: 0.0725 AC: 418 AN: 5768

European-Non Finnish (NFE) AF: 0.117 AC: 130125 AN: 1111888

Other (OTH) AF: 0.133 AC: 8008 AN: 60396

GnomAD4 genome AF: 0.229 AC: 34774 AN: 152052 Hom.: 6757 Cov.: 32 AF XY: 0.223 AC XY: 16581 AN XY: 74358

African (AFR) AF: 0.532 AC: 22007 AN: 41384

American (AMR) AF: 0.181 AC: 2772 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.0656 AC: 339 AN: 5168

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4828

European-Finnish (FIN) AF: 0.0953 AC: 1011 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7700 AN: 68000

Other (OTH) AF: 0.198 AC: 417 AN: 2108

Alfa AF: 0.150 Hom.: 4395

Bravo AF: 0.247

Asia WGS AF: 0.130 AC: 452 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.103

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	IL4R-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.91
DANN	Benign	0.62
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2234898; hg19: chr16-27373915; COSMIC: COSV50138798; COSMIC: COSV50138798;