rs3024672

Variant names:

• chr16-27361810-G-A
• rs3024672
• NM_000418.4:c.900-442G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-27361810-G-A
• chr16-27361810-G-C

Variant summary

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

The NM_000418.4(IL4R):​c.900-442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,602 control chromosomes in the GnomAD database, including 4,106 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 0.15 (4106 hom., cov: 31)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 10 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.900-442G>A		intron_variant	Intron 10 of 10	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.900-442G>A		intron_variant	Intron 10 of 10	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23223 AN: 151484 Hom.: 4090 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.154 AC: 23292 AN: 151602 Hom.: 4106 Cov.: 31 AF XY: 0.148 AC XY: 10973 AN XY: 74066

African (AFR) AF: 0.429 AC: 17711 AN: 41246

American (AMR) AF: 0.0885 AC: 1347 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3468

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5144

South Asian (SAS) AF: 0.0361 AC: 173 AN: 4792

European-Finnish (FIN) AF: 0.0281 AC: 296 AN: 10530

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3152 AN: 67898

Other (OTH) AF: 0.130 AC: 272 AN: 2092

Alfa AF: 0.0829 Hom.: 697

Bravo AF: 0.170

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-1.6
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: rs3024672; hg19: chr16-27373131;