5-132660272-A-C

Position:

• chr5-132660272-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002188.3(IL13):​c.431A>C​(p.Gln144Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL13 NM_002188.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044944704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13	NM_002188.3	c.431A>C	p.Gln144Pro	missense_variant	4/4	ENST00000304506.7	NP_002179.2
IL13	NM_001354991.2	c.236A>C	p.Gln79Pro	missense_variant	5/5		NP_001341920.1
IL13	NM_001354992.2	c.236A>C	p.Gln79Pro	missense_variant	6/6		NP_001341921.1
IL13	NM_001354993.2	c.236A>C	p.Gln79Pro	missense_variant	5/5		NP_001341922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL13	ENST00000304506.7	c.431A>C	p.Gln144Pro	missense_variant	4/4	1	NM_002188.3	ENSP00000304915	P1
TH2LCRR	ENST00000435042.1	n.94+3907T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0030
DANN	Benign	0.27
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.27	T;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.020
Sift	Benign	0.17	.;T
Sift4G	Benign	0.30	T;T
Vest4		0.16
MutPred		0.24		.;Loss of MoRF binding (P = 0.0396);
MVP		0.092
MPC		0.17
ClinPred		0.49	T
GERP RS		-7.2
gMVP		0.30

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;