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GeneBe

rs20541

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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 Genomes project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q144R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

IL13
NM_002188.3 missense

Scores

14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73
Variant links:
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)

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ACMG classification

Classification made for transcript

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 UniProt
IL13NM_002188.3 linkuse as main transcriptc.431A>C p.Gln144Pro missense_variant 4/4 ENST00000304506.7
IL13NM_001354991.2 linkuse as main transcriptc.236A>C p.Gln79Pro missense_variant 5/5
IL13NM_001354992.2 linkuse as main transcriptc.236A>C p.Gln79Pro missense_variant 6/6
IL13NM_001354993.2 linkuse as main transcriptc.236A>C p.Gln79Pro missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL13ENST00000304506.7 linkuse as main transcriptc.431A>C p.Gln144Pro missense_variant 4/41 NM_002188.3 P1
TH2LCRRENST00000435042.1 linkuse as main transcriptn.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
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs20541; hg19: chr5-131995964; API