chrX-118758225-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001560.3(IL13RA1):c.659T>C(p.Val220Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000477 in 1,047,248 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000032 ( 0 hom. 1 hem. )
Consequence
IL13RA1
NM_001560.3 missense
NM_001560.3 missense
Scores
10
7
Clinical Significance
Conservation
PhyloP100: 2.15
Genes affected
IL13RA1 (HGNC:5974): (interleukin 13 receptor subunit alpha 1) The protein encoded by this gene is a subunit of the interleukin 13 receptor. This subunit forms a receptor complex with IL4 receptor alpha, a subunit shared by IL13 and IL4 receptors. This subunit serves as a primary IL13-binding subunit of the IL13 receptor, and may also be a component of IL4 receptors. This protein has been shown to bind tyrosine kinase TYK2, and thus may mediate the signaling processes that lead to the activation of JAK1, STAT3 and STAT6 induced by IL13 and IL4. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL13RA1 | NM_001560.3 | c.659T>C | p.Val220Ala | missense_variant | 5/11 | ENST00000371666.8 | |
IL13RA1 | XM_047442096.1 | c.659T>C | p.Val220Ala | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL13RA1 | ENST00000371666.8 | c.659T>C | p.Val220Ala | missense_variant | 5/11 | 1 | NM_001560.3 | P1 | |
IL13RA1 | ENST00000371642.1 | c.659T>C | p.Val220Ala | missense_variant | 5/6 | 1 | |||
IL13RA1 | ENST00000652600.1 | c.653T>C | p.Val218Ala | missense_variant | 6/12 | ||||
IL13RA1 | ENST00000481868.1 | n.247T>C | non_coding_transcript_exon_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111984Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34162
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GnomAD3 exomes AF: 0.0000116 AC: 2AN: 173153Hom.: 0 AF XY: 0.0000168 AC XY: 1AN XY: 59377
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GnomAD4 exome AF: 0.00000321 AC: 3AN: 935264Hom.: 0 Cov.: 17 AF XY: 0.00000399 AC XY: 1AN XY: 250854
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The c.659T>C (p.V220A) alteration is located in exon 5 (coding exon 5) of the IL13RA1 gene. This alteration results from a T to C substitution at nucleotide position 659, causing the valine (V) at amino acid position 220 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of stability (P = 0.0577);Loss of stability (P = 0.0577);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at