NM_000418.4:c.671-630A>G

Variant names:

• chr16-27355178-A-G
• rs3024633
• NM_000418.4:c.671-630A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000418.4(IL4R):​c.671-630A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 328,324 control chromosomes in the GnomAD database, including 919 homozygotes. 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 0.072 (446 hom., cov: 32)
  • Exomes 𝑓: 0.065 (473 hom.)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0817 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	NM_000418.4	MANE Select	c.671-630A>G		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.671-630A>G		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.626-630A>G		intron	N/A	NP_001244336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.671-630A>G		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.671-630A>G		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.626-630A>G		intron	N/A	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10870 AN: 152080 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0739

GnomAD4 exome AF: 0.0655 AC: 11532 AN: 176126 Hom.: 473 AF XY: 0.0634 AC XY: 6177 AN XY: 97420

African (AFR) AF: 0.0670 AC: 319 AN: 4762

American (AMR) AF: 0.0396 AC: 546 AN: 13802

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 439 AN: 4266

East Asian (EAS) AF: 0.000299 AC: 2 AN: 6698

South Asian (SAS) AF: 0.0493 AC: 1850 AN: 37540

European-Finnish (FIN) AF: 0.0650 AC: 1053 AN: 16212

Middle Eastern (MID) AF: 0.107 AC: 224 AN: 2100

European-Non Finnish (NFE) AF: 0.0785 AC: 6513 AN: 82964

Other (OTH) AF: 0.0753 AC: 586 AN: 7782

GnomAD4 genome AF: 0.0715 AC: 10883 AN: 152198 Hom.: 446 Cov.: 32 AF XY: 0.0701 AC XY: 5218 AN XY: 74408

African (AFR) AF: 0.0668 AC: 2772 AN: 41520

American (AMR) AF: 0.0573 AC: 875 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 343 AN: 3464

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4828

European-Finnish (FIN) AF: 0.0735 AC: 778 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0835 AC: 5678 AN: 68014

Other (OTH) AF: 0.0731 AC: 154 AN: 2106

Alfa AF: 0.0810 Hom.: 835

Bravo AF: 0.0703

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.59
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: rs3024633; hg19: chr16-27366499;