16-27344896-C-T

Variant names:

• chr16-27344896-C-T
• rs145184963
• NM_000418.4:c.237C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001257997.2(IL4R):​c.-239C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,614,150 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (17 hom.)
• Consequence: IL4R NM_001257997.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-27344896-C-T is Benign according to our data. Variant chr16-27344896-C-T is described in ClinVar as Benign. ClinVar VariationId is 718605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0065 (990/152318) while in subpopulation AFR AF = 0.0227 (944/41570). AF 95% confidence interval is 0.0215. There are 18 homozygotes in GnomAd4. There are 492 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257997.2. 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.237C>T	p.Asn79Asn	synonymous	Exon 5 of 11	NP_000409.1	P24394-1
	IL4R	NM_001257997.2		c.-239C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 10	NP_001244926.1
	IL4R	NM_001257406.2		c.237C>T	p.Asn79Asn	synonymous	Exon 4 of 10	NP_001244335.1	P24394-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL4R	ENST00000395762.7	TSL:1 MANE Select	c.237C>T	p.Asn79Asn	synonymous	Exon 5 of 11	ENSP00000379111.2	P24394-1
	IL4R	ENST00000543915.6	TSL:1	c.237C>T	p.Asn79Asn	synonymous	Exon 4 of 10	ENSP00000441667.2	P24394-1
	IL4R	ENST00000912076.1		c.258C>T	p.Asn86Asn	synonymous	Exon 4 of 10	ENSP00000582135.1

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 988 AN: 152200 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

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: 0.000147

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00193 AC: 485 AN: 251198 AF XY: 0.00152

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000983 AC: 1437 AN: 1461832 Hom.: 17 Cov.: 40 AF XY: 0.000853 AC XY: 620 AN XY: 727218

African (AFR) AF: 0.0272 AC: 909 AN: 33476

American (AMR) AF: 0.00121 AC: 54 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: 0.000162 AC: 14 AN: 86256

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53384

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5766

European-Non Finnish (NFE) AF: 0.000303 AC: 337 AN: 1111998

Other (OTH) AF: 0.00185 AC: 112 AN: 60392

GnomAD4 genome AF: 0.00650 AC: 990 AN: 152318 Hom.: 18 Cov.: 32 AF XY: 0.00661 AC XY: 492 AN XY: 74470

African (AFR) AF: 0.0227 AC: 944 AN: 41570

American (AMR) AF: 0.00163 AC: 25 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00567 Hom.: 6

Bravo AF: 0.00813

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

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	-0.82
CADD	Benign	1.0
DANN	Benign	0.77
PhyloP100		-1.7
PromoterAI		0.0090	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: rs145184963; hg19: chr16-27356217;