5-132660151-T-C

Variant names:

• chr5-132660151-T-C
• rs1295686
• NM_002188.3:c.334-24T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002188.3(IL13):​c.334-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 1,609,364 control chromosomes in the GnomAD database, including 471,012 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 0.63 (33058 hom., cov: 32)
  • Exomes 𝑓: 0.77 (437954 hom.)
• Consequence: IL13 NM_002188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 221 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13	NM_002188.3	c.334-24T>C		intron_variant	Intron 3 of 3	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.139-24T>C		intron_variant	Intron 4 of 4		NP_001341920.1
IL13	NM_001354992.2	c.139-24T>C		intron_variant	Intron 5 of 5		NP_001341921.1
IL13	NM_001354993.2	c.139-24T>C		intron_variant	Intron 4 of 4		NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7	c.334-24T>C		intron_variant	Intron 3 of 3	1	NM_002188.3	ENSP00000304915.3

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95834 AN: 151944 Hom.: 33064 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.677

GnomAD2 exomes AF: 0.679 AC: 169794 AN: 250072 AF XY: 0.698

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.741

Gnomad EAS exome AF: 0.673

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.728

GnomAD4 exome AF: 0.768 AC: 1118945 AN: 1457302 Hom.: 437954 Cov.: 30 AF XY: 0.768 AC XY: 556806 AN XY: 725290

African (AFR) AF: 0.338 AC: 11282 AN: 33356

American (AMR) AF: 0.461 AC: 20498 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 19357 AN: 26090

East Asian (EAS) AF: 0.683 AC: 27078 AN: 39662

South Asian (SAS) AF: 0.690 AC: 59350 AN: 86064

European-Finnish (FIN) AF: 0.628 AC: 33403 AN: 53180

Middle Eastern (MID) AF: 0.719 AC: 4144 AN: 5760

European-Non Finnish (NFE) AF: 0.811 AC: 899009 AN: 1108454

Other (OTH) AF: 0.744 AC: 44824 AN: 60228

GnomAD4 genome AF: 0.630 AC: 95842 AN: 152062 Hom.: 33058 Cov.: 32 AF XY: 0.624 AC XY: 46356 AN XY: 74316

African (AFR) AF: 0.347 AC: 14394 AN: 41472

American (AMR) AF: 0.606 AC: 9256 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2535 AN: 3466

East Asian (EAS) AF: 0.672 AC: 3470 AN: 5160

South Asian (SAS) AF: 0.692 AC: 3335 AN: 4818

European-Finnish (FIN) AF: 0.611 AC: 6456 AN: 10564

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 53954 AN: 67978

Other (OTH) AF: 0.679 AC: 1437 AN: 2116

Alfa AF: 0.737 Hom.: 167126

Bravo AF: 0.614

Asia WGS AF: 0.650 AC: 2261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.61
DANN	Benign	0.21
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1295686; hg19: chr5-131995843; COSMIC: COSV58734285; COSMIC: COSV58734285;