rs848

Positions:

• chr5-132660808-A-C
• chr5-132660808-A-G

Variant summary

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

The NM_002188.3(IL13):​c.*526A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 158,878 control chromosomes in the GnomAD database, including 38,217 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 0.68 (36320 hom., cov: 31)
  • Exomes 𝑓: 0.72 (1897 hom.)
• Consequence: IL13 NM_002188.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_002188.3	c.*526A>C		3_prime_UTR_variant	4/4	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.*526A>C		3_prime_UTR_variant	5/5		NP_001341920.1
IL13	NM_001354992.2	c.*526A>C		3_prime_UTR_variant	6/6		NP_001341921.1
IL13	NM_001354993.2	c.*526A>C		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.*526A>C		3_prime_UTR_variant	4/4	1	NM_002188.3	ENSP00000304915.3
TH2LCRR	ENST00000435042.1	n.94+3371T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102993 AN: 151830 Hom.: 36321 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.718

GnomAD4 exome AF: 0.721 AC: 4995 AN: 6932 Hom.: 1897 Cov.: 0 AF XY: 0.719 AC XY: 2635 AN XY: 3666

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.840

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.822

Gnomad4 OTH exome AF: 0.742

GnomAD4 genome AF: 0.678 AC: 103020 AN: 151946 Hom.: 36320 Cov.: 31 AF XY: 0.671 AC XY: 49826 AN XY: 74242

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.719

Alfa AF: 0.778 Hom.: 42234

Bravo AF: 0.669

Asia WGS AF: 0.665 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.75

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: rs848; hg19: chr5-131996500;