5-132660197-G-A

Position:

• chr5-132660197-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002188.3(IL13):​c.356G>A​(p.Arg119Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,614,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: IL13 NM_002188.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.255

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0073035657).
• BP6: Variant 5-132660197-G-A is Benign according to our data. Variant chr5-132660197-G-A is described in ClinVar as [Benign]. Clinvar id is 3045158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13	NM_002188.3	c.356G>A	p.Arg119Gln	missense_variant	4/4	ENST00000304506.7
IL13	NM_001354991.2	c.161G>A	p.Arg54Gln	missense_variant	5/5
IL13	NM_001354992.2	c.161G>A	p.Arg54Gln	missense_variant	6/6
IL13	NM_001354993.2	c.161G>A	p.Arg54Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13	ENST00000304506.7	c.356G>A	p.Arg119Gln	missense_variant	4/4	1	NM_002188.3	P1
TH2LCRR	ENST00000435042.1	n.94+3982C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 273 AN: 152180 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00591

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000525 AC: 132 AN: 251396 Hom.: 0 AF XY: 0.000419 AC XY: 57 AN XY: 135894

Gnomad AFR exome AF: 0.00578

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000276 AC: 403 AN: 1461842 Hom.: 0 Cov.: 37 AF XY: 0.000260 AC XY: 189 AN XY: 727222

Gnomad4 AFR exome AF: 0.00541

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152298 Hom.: 2 Cov.: 33 AF XY: 0.00185 AC XY: 138 AN XY: 74482

Gnomad4 AFR AF: 0.00594

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000395 Hom.: 0

Bravo AF: 0.00222

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000717 AC: 87

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

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

Nov 07, 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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.3
DANN	Uncertain	0.98
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.73	T;.
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0073	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
Sift4G	Benign	0.38	T;T
Vest4		0.086
MVP		0.37
MPC		0.18
ClinPred		0.0069	T
GERP RS		-2.4
gMVP		0.065

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: rs140828306; hg19: chr5-131995889;