16-27360628-A-T

Variant names:

• chr16-27360628-A-T
• rs3024668
• NM_000418.4:c.850-138A>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.850-138A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL4R NM_000418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 14 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=-0.87).

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.850-138A>T		intron	N/A	NP_000409.1
	IL4R	NM_001257406.2		c.850-138A>T		intron	N/A	NP_001244335.1
	IL4R	NM_001257407.2		c.805-138A>T		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.850-138A>T		intron	N/A	ENSP00000379111.2
	IL4R	ENST00000543915.6	TSL:1	c.850-138A>T		intron	N/A	ENSP00000441667.2
	IL4R	ENST00000170630.6	TSL:5	c.805-138A>T		intron	N/A	ENSP00000170630.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 859092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 447780

African (AFR) AF: 0.00 AC: 0 AN: 21180

American (AMR) AF: 0.00 AC: 0 AN: 39102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20610

East Asian (EAS) AF: 0.00 AC: 0 AN: 36732

South Asian (SAS) AF: 0.00 AC: 0 AN: 70578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2860

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 579836

Other (OTH) AF: 0.00 AC: 0 AN: 39980

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.80
PhyloP100		0.12

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: rs3024668; hg19: chr16-27371949;