NM_000418.4:c.513+159A>C

Variant names:

• chr16-27346777-A-C
• rs2301807
• NM_000418.4:c.513+159A>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.513+159A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,238 control chromosomes in the GnomAD database, including 70,004 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 0.96 (70004 hom., cov: 31)
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL4R	NM_000418.4	c.513+159A>C		intron_variant	Intron 6 of 10	ENST00000395762.7	NP_000409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL4R	ENST00000395762.7	c.513+159A>C		intron_variant	Intron 6 of 10	1	NM_000418.4	ENSP00000379111.2

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145833 AN: 152120 Hom.: 69942 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.959 AC: 145954 AN: 152238 Hom.: 70004 Cov.: 31 AF XY: 0.958 AC XY: 71277 AN XY: 74402

African (AFR) AF: 0.984 AC: 40882 AN: 41550

American (AMR) AF: 0.966 AC: 14776 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3419 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4718 AN: 5164

South Asian (SAS) AF: 0.954 AC: 4603 AN: 4824

European-Finnish (FIN) AF: 0.921 AC: 9758 AN: 10596

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64555 AN: 68018

Other (OTH) AF: 0.969 AC: 2046 AN: 2112

Alfa AF: 0.953 Hom.: 23880

Bravo AF: 0.964

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.43
PhyloP100		-0.50
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: rs2301807; hg19: chr16-27358098;