chr16-27344950-T-C

Variant names:

• chr16-27344950-T-C
• rs112497527
• NM_000418.4:c.291T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000418.4(IL4R):​c.291T>C​(p.Asp97Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,614,058 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (50 hom.)
• Consequence: IL4R NM_000418.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.659
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-27344950-T-C is Benign according to our data. Variant chr16-27344950-T-C is described in ClinVar as Benign. ClinVar VariationId is 778606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.659 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0132 (2014/152266) while in subpopulation AFR AF = 0.0454 (1885/41552). AF 95% confidence interval is 0.0437. There are 52 homozygotes in GnomAd4. There are 987 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	NM_000418.4	MANE Select	c.291T>C	p.Asp97Asp	synonymous	Exon 5 of 11	NP_000409.1	P24394-1
	IL4R	NM_001257406.2		c.291T>C	p.Asp97Asp	synonymous	Exon 4 of 10	NP_001244335.1	P24394-1
	IL4R	NM_001257407.2		c.246T>C	p.Asp82Asp	synonymous	Exon 5 of 11	NP_001244336.1	P24394-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.291T>C	p.Asp97Asp	synonymous	Exon 5 of 11	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.291T>C	p.Asp97Asp	synonymous	Exon 4 of 10	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.312T>C	p.Asp104Asp	synonymous	Exon 4 of 10	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2006 AN: 152148 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00358 AC: 901 AN: 251332 AF XY: 0.00275

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.00315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00157 AC: 2289 AN: 1461792 Hom.: 50 Cov.: 40 AF XY: 0.00138 AC XY: 1000 AN XY: 727188

African (AFR) AF: 0.0510 AC: 1708 AN: 33476

American (AMR) AF: 0.00333 AC: 149 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000124 AC: 138 AN: 1111996

Other (OTH) AF: 0.00429 AC: 259 AN: 60394

GnomAD4 genome AF: 0.0132 AC: 2014 AN: 152266 Hom.: 52 Cov.: 32 AF XY: 0.0133 AC XY: 987 AN XY: 74462

African (AFR) AF: 0.0454 AC: 1885 AN: 41552

American (AMR) AF: 0.00609 AC: 93 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68016

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00852 Hom.: 22

Bravo AF: 0.0158

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.54
PhyloP100		0.66
PromoterAI		0.028	Neutral
Mutation Taster		=100/0	polymorphism

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: rs112497527; hg19: chr16-27356271;