rs20541

Variant names:

• chr5-132660272-A-G
• rs20541
• NM_002188.3:c.431A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-132660272-A-G
• chr5-132660272-A-C
• chr5-132660272-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000435042.1(TH2LCRR):​n.94+3907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,613,648 control chromosomes in the GnomAD database, including 502,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.77 (45613 hom., cov: 33)
  • Exomes 𝑓: 0.79 (456594 hom.)
• Consequence: TH2LCRR ENST00000435042.1 intron
• Clinical Significance: Benign; risk factor no assertion criteria provided B:1 O:2
• Conservation: PhyloP100: -2.73
• Publications: 623 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.8788516E-7).
• BP6: Variant 5-132660272-A-G is Benign according to our data. Variant chr5-132660272-A-G is described in ClinVar as Benign|risk_factor. ClinVar VariationId is 14673.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435042.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	NM_002188.3	MANE Select	c.431A>G	p.Gln144Arg	missense	Exon 4 of 4	NP_002179.2
	IL13	NM_001354991.2		c.236A>G	p.Gln79Arg	missense	Exon 5 of 5	NP_001341920.1	Q4VB53
	IL13	NM_001354992.2		c.236A>G	p.Gln79Arg	missense	Exon 6 of 6	NP_001341921.1	Q4VB53

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13	ENST00000304506.7	TSL:1 MANE Select	c.431A>G	p.Gln144Arg	missense	Exon 4 of 4	ENSP00000304915.3	P35225
	IL13	ENST00000462480.1	TSL:1	n.1502A>G		non_coding_transcript_exon	Exon 3 of 3
	IL13	ENST00000459878.5	TSL:3	n.435A>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117104 AN: 152080 Hom.: 45591 Cov.: 33

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.782

GnomAD2 exomes AF: 0.721 AC: 180758 AN: 250830 AF XY: 0.730

Gnomad AFR exome AF: 0.816

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.673

Gnomad FIN exome AF: 0.623

Gnomad NFE exome AF: 0.805

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.786 AC: 1149254 AN: 1461450 Hom.: 456594 Cov.: 62 AF XY: 0.785 AC XY: 570680 AN XY: 727054

African (AFR) AF: 0.821 AC: 27477 AN: 33476

American (AMR) AF: 0.497 AC: 22184 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 20330 AN: 26132

East Asian (EAS) AF: 0.681 AC: 27036 AN: 39688

South Asian (SAS) AF: 0.709 AC: 61157 AN: 86236

European-Finnish (FIN) AF: 0.628 AC: 33408 AN: 53200

Middle Eastern (MID) AF: 0.787 AC: 4538 AN: 5764

European-Non Finnish (NFE) AF: 0.815 AC: 905775 AN: 1111898

Other (OTH) AF: 0.784 AC: 47349 AN: 60384

GnomAD4 genome AF: 0.770 AC: 117176 AN: 152198 Hom.: 45613 Cov.: 33 AF XY: 0.759 AC XY: 56459 AN XY: 74410

African (AFR) AF: 0.817 AC: 33936 AN: 41534

American (AMR) AF: 0.670 AC: 10242 AN: 15292

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

East Asian (EAS) AF: 0.672 AC: 3482 AN: 5182

South Asian (SAS) AF: 0.710 AC: 3416 AN: 4810

European-Finnish (FIN) AF: 0.611 AC: 6471 AN: 10586

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54278 AN: 68008

Other (OTH) AF: 0.783 AC: 1654 AN: 2112

Alfa AF: 0.789 Hom.: 235883

Bravo AF: 0.775

TwinsUK AF: 0.815 AC: 3021

ALSPAC AF: 0.820 AC: 3159

ESP6500AA AF: 0.828 AC: 3647

ESP6500EA AF: 0.805 AC: 6923

ExAC AF: 0.733 AC: 88995

Asia WGS AF: 0.690 AC: 2400 AN: 3478

EpiCase AF: 0.811

EpiControl AF: 0.817

ClinVar

ClinVar submissions

Significance: Benign; risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	IL13-related disorder (1)
-	-	-	Allergic rhinitis, susceptibility to (1)
-	-	-	Inherited susceptibility to asthma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0020
DANN	Benign	0.18
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-1.1	T
PhyloP100		-2.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.0080
Sift	Benign	1.0	T
Sift4G	Benign	0.58	T
Vest4		0.013
MPC		0.15
ClinPred		0.016	T
GERP RS		-7.2
gMVP		0.054
Mutation Taster		=99/1	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: rs20541; hg19: chr5-131995964; COSMIC: COSV58734609; COSMIC: COSV58734609;