rs1295685

Positions:

• chr5-132660753-A-G
• chr5-132660753-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002188.3(IL13):​c.*471A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 167,038 control chromosomes in the GnomAD database, including 54,304 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 0.80 (50132 hom., cov: 31)
  • Exomes 𝑓: 0.73 (4172 hom.)
• Consequence: IL13 NM_002188.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

Genes affected

IL13 (HGNC:5973): (interleukin 13) This gene encodes an immunoregulatory cytokine produced primarily by activated Th2 cells. This cytokine is involved in several stages of B-cell maturation and differentiation. It up-regulates CD23 and MHC class II expression, and promotes IgE isotype switching of B cells. This cytokine down-regulates macrophage activity, thereby inhibits the production of pro-inflammatory cytokines and chemokines. This cytokine is found to be critical to the pathogenesis of allergen-induced asthma but operates through mechanisms independent of IgE and eosinophils. This gene, IL3, IL5, IL4, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL4. [provided by RefSeq, Jul 2008]

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_002188.3	c.*471A>G		3_prime_UTR_variant	4/4	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.*471A>G		3_prime_UTR_variant	5/5		NP_001341920.1
IL13	NM_001354992.2	c.*471A>G		3_prime_UTR_variant	6/6		NP_001341921.1
IL13	NM_001354993.2	c.*471A>G		3_prime_UTR_variant	5/5		NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7	c.*471A>G		3_prime_UTR_variant	4/4	1	NM_002188.3	ENSP00000304915	P1
TH2LCRR	ENST00000435042.1	n.94+3426T>C		intron_variant, non_coding_transcript_variant		5
IL13	ENST00000487267.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122230 AN: 152012 Hom.: 50082 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.803

GnomAD4 exome AF: 0.734 AC: 10946 AN: 14908 Hom.: 4172 Cov.: 0 AF XY: 0.736 AC XY: 5818 AN XY: 7910

Gnomad4 AFR exome AF: 0.939

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.824

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.795

GnomAD4 genome AF: 0.804 AC: 122339 AN: 152130 Hom.: 50132 Cov.: 31 AF XY: 0.792 AC XY: 58868 AN XY: 74352

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.804

Alfa AF: 0.805 Hom.: 45285

Bravo AF: 0.814

Asia WGS AF: 0.701 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs1295685; hg19: chr5-131996445;