rs2069744

Positions:

• chr5-132658977-C-T

Variant summary

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

The NM_002188.3(IL13):​c.175-441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 202,282 control chromosomes in the GnomAD database, including 1,884 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 0.091 (1743 hom., cov: 32)
  • Exomes 𝑓: 0.031 (141 hom.)
• Consequence: IL13 NM_002188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_002188.3	c.175-441C>T		intron_variant		ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.-21-441C>T		intron_variant			NP_001341920.1
IL13	NM_001354992.2	c.-21-441C>T		intron_variant			NP_001341921.1
IL13	NM_001354993.2	c.-21-441C>T		intron_variant			NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7	c.175-441C>T		intron_variant		1	NM_002188.3	ENSP00000304915	P1
TH2LCRR	ENST00000435042.1	n.94+5202G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13859 AN: 152050 Hom.: 1728 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.0732

GnomAD4 exome AF: 0.0305 AC: 1529 AN: 50114 Hom.: 141 Cov.: 0 AF XY: 0.0283 AC XY: 728 AN XY: 25764

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.0665

Gnomad4 ASJ exome AF: 0.0243

Gnomad4 EAS exome AF: 0.0860

Gnomad4 SAS exome AF: 0.00542

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.00321

Gnomad4 OTH exome AF: 0.0247

GnomAD4 genome AF: 0.0915 AC: 13917 AN: 152168 Hom.: 1743 Cov.: 32 AF XY: 0.0898 AC XY: 6682 AN XY: 74400

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0931

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.00366

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0617 Hom.: 183

Bravo AF: 0.105

Asia WGS AF: 0.0670 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.53

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: rs2069744; hg19: chr5-131994669;