chrX-118766531-T-G

Variant names:

• chrX-118766531-T-G
• NM_001560.3:c.830T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001560.3(IL13RA1):​c.830T>G​(p.Val277Gly) variant causes a missense, splice region 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. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: IL13RA1 NM_001560.3 missense, splice_region
• Scores: Splicing: ADA: 0.0004486
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34825778).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001560.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13RA1	NM_001560.3	MANE Select	c.830T>G	p.Val277Gly	missense splice_region	Exon 7 of 11	NP_001551.1	P78552-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL13RA1	ENST00000371666.8	TSL:1 MANE Select	c.830T>G	p.Val277Gly	missense splice_region	Exon 7 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000965042.1		c.971T>G	p.Val324Gly	missense splice_region	Exon 8 of 12	ENSP00000635101.1
	IL13RA1	ENST00000865793.1		c.830T>G	p.Val277Gly	missense splice_region	Exon 7 of 12	ENSP00000535852.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.53
Sift	Benign	0.12	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.25	B
Vest4		0.35
MutPred		0.66		Loss of stability (P = 0.025)
MVP		0.91
MPC		0.27
ClinPred		0.18	T
GERP RS		1.8
Varity_R		0.58
gMVP		0.74
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-117900494;