16-27364221-G-T

Variant names:

• chr16-27364221-G-T
• rs1049631
• NM_000418.4:c.*391G>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.*391G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 180,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: IL4R NM_000418.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 21 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 (BayesDel_noAF=-0.84).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	NM_000418.4	MANE Select	c.*391G>T		3_prime_UTR	Exon 11 of 11	NP_000409.1
	IL4R	NM_001257406.2		c.*391G>T		3_prime_UTR	Exon 10 of 10	NP_001244335.1
	IL4R	NM_001257407.2		c.*391G>T		3_prime_UTR	Exon 11 of 11	NP_001244336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.*391G>T		3_prime_UTR	Exon 11 of 11	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.*391G>T		3_prime_UTR	Exon 10 of 10	ENSP00000441667.2
	IL4R	ENST00000565352.1	TSL:5	c.348G>T	p.Thr116Thr	synonymous	Exon 5 of 5	ENSP00000461268.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151966 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000674 AC: 3 AN: 4452 AF XY: 0.000913

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000178 AC: 5 AN: 28142 Hom.: 0 Cov.: 0 AF XY: 0.000142 AC XY: 2 AN XY: 14132

African (AFR) AF: 0.00 AC: 0 AN: 992

American (AMR) AF: 0.00 AC: 0 AN: 1870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 940

East Asian (EAS) AF: 0.00 AC: 0 AN: 1492

South Asian (SAS) AF: 0.00 AC: 0 AN: 1054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.000214 AC: 4 AN: 18722

Other (OTH) AF: 0.000585 AC: 1 AN: 1710

GnomAD4 genome AF: 0.000105 AC: 16 AN: 151966 Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6 AN XY: 74218

African (AFR) AF: 0.0000725 AC: 3 AN: 41368

American (AMR) AF: 0.000328 AC: 5 AN: 15242

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67986

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

Alfa AF: 0.00 Hom.: 38377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
DANN	Benign	0.40
PhyloP100		-0.34

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: rs1049631; hg19: chr16-27375542;