rs2069743

Positions:

• chr5-132657583-A-G

Variant summary

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

The NM_001354991.2(IL13):​c.-92-707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 152,226 control chromosomes in the GnomAD database, including 764 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 0.055 (764 hom., cov: 32)
• Consequence: IL13 NM_001354991.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_001354991.2	c.-92-707A>G		intron_variant			NP_001341920.1
IL13	NM_001354992.2	c.-93+339A>G		intron_variant			NP_001341921.1
IL13	NM_001354993.2	c.-22+339A>G		intron_variant			NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TH2LCRR	ENST00000435042.1	n.94+6596T>C		intron_variant		5
IL13	ENST00000459878.5	n.108-707A>G		intron_variant		3
IL13	ENST00000468334.5	n.547+339A>G		intron_variant		3
IL13	ENST00000487267.5	n.274+339A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8374 AN: 152108 Hom.: 766 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.0325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0551 AC: 8382 AN: 152226 Hom.: 764 Cov.: 32 AF XY: 0.0541 AC XY: 4026 AN XY: 74446

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.0321

Alfa AF: 0.0651 Hom.: 103

Bravo AF: 0.0626

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.8
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2069743; hg19: chr5-131993275;