NM_000418.4:c.670+789G>A

Variant names:

• chr16-27353485-G-A
• rs3024619
• NM_000418.4:c.670+789G>A

Variant summary

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

The NM_000418.4(IL4R):​c.670+789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,914 control chromosomes in the GnomAD database, including 8,302 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 0.32 (8302 hom., cov: 32)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 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.670+789G>A		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.670+789G>A		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.625+789G>A		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.670+789G>A		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.670+789G>A		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.625+789G>A		intron	N/A	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48608 AN: 151794 Hom.: 8291 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48649 AN: 151914 Hom.: 8302 Cov.: 32 AF XY: 0.324 AC XY: 24042 AN XY: 74266

African (AFR) AF: 0.206 AC: 8525 AN: 41452

American (AMR) AF: 0.386 AC: 5884 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2408 AN: 5164

South Asian (SAS) AF: 0.464 AC: 2231 AN: 4808

European-Finnish (FIN) AF: 0.331 AC: 3476 AN: 10504

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23910 AN: 67944

Other (OTH) AF: 0.323 AC: 681 AN: 2106

Alfa AF: 0.341 Hom.: 14049

Bravo AF: 0.319

Asia WGS AF: 0.463 AC: 1608 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		0.40
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: rs3024619; hg19: chr16-27364806;