rs141903283

Variant names:

• chr16-27345014-G-A
• rs141903283
• NM_000418.4:c.355G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-27345014-G-A
• chr16-27345014-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000418.4(IL4R):​c.355G>A​(p.Glu119Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,586,516 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: IL4R NM_000418.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02783522).

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.355G>A	p.Glu119Lys	missense	Exon 5 of 11	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.355G>A	p.Glu119Lys	missense	Exon 4 of 10	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.310G>A	p.Glu104Lys	missense	Exon 5 of 11	NP_001244336.1	P24394-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.355G>A	p.Glu119Lys	missense	Exon 5 of 11	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.355G>A	p.Glu119Lys	missense	Exon 4 of 10	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.376G>A	p.Glu126Lys	missense	Exon 4 of 10	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.000304 AC: 46 AN: 151454 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000960

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000590

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000300 AC: 75 AN: 250352 AF XY: 0.000295

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000599

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000410 AC: 588 AN: 1435062 Hom.: 1 Cov.: 41 AF XY: 0.000404 AC XY: 288 AN XY: 713562

African (AFR) AF: 0.0000610 AC: 2 AN: 32802

American (AMR) AF: 0.000182 AC: 8 AN: 43872

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25254

East Asian (EAS) AF: 0.00 AC: 0 AN: 38070

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86008

European-Finnish (FIN) AF: 0.0000598 AC: 3 AN: 50160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.000511 AC: 559 AN: 1094574

Other (OTH) AF: 0.000238 AC: 14 AN: 58722

GnomAD4 genome AF: 0.000304 AC: 46 AN: 151454 Hom.: 0 Cov.: 32 AF XY: 0.000257 AC XY: 19 AN XY: 73958

African (AFR) AF: 0.0000242 AC: 1 AN: 41352

American (AMR) AF: 0.000197 AC: 3 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.0000960 AC: 1 AN: 10412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000590 AC: 40 AN: 67812

Other (OTH) AF: 0.000480 AC: 1 AN: 2082

Alfa AF: 0.000589 Hom.: 0

Bravo AF: 0.000325

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000354 AC: 43

EpiCase AF: 0.000709

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	3.4
DANN	Benign	0.91
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.25	T
Sift4G	Benign	0.43	T
Polyphen		0.10	B
Vest4		0.11
MVP		0.39
MPC		0.15
ClinPred		0.026	T
GERP RS		-6.2
PromoterAI		0.032	Neutral
Varity_R		0.13
gMVP		0.44
Mutation Taster		=87/13	polymorphism

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: rs141903283; hg19: chr16-27356335;