5-132660272-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002188.3(IL13):c.431A>G(p.Gln144Arg) variant causes a missense 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45613 hom., cov: 33)
  • Exomes 𝑓: 0.79 (456594 hom.)
• Consequence: IL13 NM_002188.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:2
• Conservation: PhyloP100: -2.73

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

Verdict is Benign. Variant got -14 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]. Clinvar id is 14673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13	NM_002188.3	c.431A>G	p.Gln144Arg	missense_variant	4/4	ENST00000304506.7
IL13	NM_001354991.2	c.236A>G	p.Gln79Arg	missense_variant	5/5
IL13	NM_001354992.2	c.236A>G	p.Gln79Arg	missense_variant	6/6
IL13	NM_001354993.2	c.236A>G	p.Gln79Arg	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13	ENST00000304506.7	c.431A>G	p.Gln144Arg	missense_variant	4/4	1	NM_002188.3	P1
TH2LCRR	ENST00000435042.1	n.94+3907T>C		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.721 AC: 180758 AN: 250830 Hom.: 67299 AF XY: 0.730 AC XY: 99024 AN XY: 135632

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 SAS exome AF: 0.711

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

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.778

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.784

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

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.783

Alfa AF: 0.791 Hom.: 120882

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

Significance: Benign

Submissions summary: Benign:1 Other:2

Revision: criteria provided, single submitter

Submissions by phenotype

IL13-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inherited susceptibility to asthma Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2005

- -

Allergic rhinitis, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

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;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.23	T
Sift4G	Benign	0.58	T;T
Vest4		0.013
MPC		0.15
ClinPred		0.016	T
GERP RS		-7.2
gMVP		0.054

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: rs20541; hg19: chr5-131995964; COSMIC: COSV58734609; COSMIC: COSV58734609;