chr5-132660753-A-G

Variant names:

• chr5-132660753-A-G
• rs1295685
• NM_002188.3:c.*471A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 100 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002188.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	NM_002188.3	MANE Select	c.*471A>G		3_prime_UTR	Exon 4 of 4	NP_002179.2
	IL13	NM_001354991.2		c.*471A>G		3_prime_UTR	Exon 5 of 5	NP_001341920.1
	IL13	NM_001354992.2		c.*471A>G		3_prime_UTR	Exon 6 of 6	NP_001341921.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	ENST00000304506.7	TSL:1 MANE Select	c.*471A>G		3_prime_UTR	Exon 4 of 4	ENSP00000304915.3
	TH2LCRR	ENST00000435042.1	TSL:5	n.94+3426T>C		intron	N/A
	IL13	ENST00000459878.5	TSL:3	n.*139A>G		downstream_gene	N/A

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

African (AFR) AF: 0.939 AC: 248 AN: 264

American (AMR) AF: 0.564 AC: 1537 AN: 2724

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 173 AN: 210

East Asian (EAS) AF: 0.677 AC: 670 AN: 990

South Asian (SAS) AF: 0.709 AC: 1305 AN: 1840

European-Finnish (FIN) AF: 0.640 AC: 371 AN: 580

Middle Eastern (MID) AF: 0.769 AC: 20 AN: 26

European-Non Finnish (NFE) AF: 0.801 AC: 6153 AN: 7684

Other (OTH) AF: 0.795 AC: 469 AN: 590

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

African (AFR) AF: 0.938 AC: 38946 AN: 41534

American (AMR) AF: 0.678 AC: 10361 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2664 AN: 3470

East Asian (EAS) AF: 0.674 AC: 3483 AN: 5166

South Asian (SAS) AF: 0.711 AC: 3425 AN: 4818

European-Finnish (FIN) AF: 0.611 AC: 6457 AN: 10562

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54268 AN: 67986

Other (OTH) AF: 0.804 AC: 1699 AN: 2112

Alfa AF: 0.806 Hom.: 59338

Bravo AF: 0.814

Asia WGS AF: 0.701 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1295685; hg19: chr5-131996445;