rs760024863

Variant names:

• chrX-118758117-G-A
• rs760024863
• NM_001560.3:c.551G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001560.3(IL13RA1):​c.551G>A​(p.Gly184Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,168,277 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 48 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.00015 (0 hom. 46 hem.)
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.257
• 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: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant X-118758117-G-A is Benign according to our data. Variant chrX-118758117-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 754602.
• BS2: High Hemizygotes in GnomAd4 at 2 gene

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.551G>A	p.Gly184Asp	missense	Exon 5 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.551G>A	p.Gly184Asp	missense	Exon 5 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000371642.1	TSL:1	c.551G>A	p.Gly184Asp	missense	Exon 5 of 6	ENSP00000360705.1	P78552-2
	IL13RA1	ENST00000965042.1		c.692G>A	p.Gly231Asp	missense	Exon 6 of 12	ENSP00000635101.1

Frequencies

GnomAD3 genomes AF: 0.0000536 AC: 6 AN: 111940 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000939

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000350 AC: 64 AN: 183075 AF XY: 0.000311

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000250

Gnomad NFE exome AF: 0.000709

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.000154 AC: 163 AN: 1056337 Hom.: 0 Cov.: 24 AF XY: 0.000140 AC XY: 46 AN XY: 328123

African (AFR) AF: 0.00 AC: 0 AN: 25790

American (AMR) AF: 0.00 AC: 0 AN: 34943

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18908

East Asian (EAS) AF: 0.00 AC: 0 AN: 29729

South Asian (SAS) AF: 0.00 AC: 0 AN: 51656

European-Finnish (FIN) AF: 0.000324 AC: 13 AN: 40106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4013

European-Non Finnish (NFE) AF: 0.000167 AC: 135 AN: 806760

Other (OTH) AF: 0.000338 AC: 15 AN: 44432

GnomAD4 genome AF: 0.0000536 AC: 6 AN: 111940 Hom.: 0 Cov.: 22 AF XY: 0.0000587 AC XY: 2 AN XY: 34096

African (AFR) AF: 0.00 AC: 0 AN: 30829

American (AMR) AF: 0.00 AC: 0 AN: 10495

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2708

European-Finnish (FIN) AF: 0.000166 AC: 1 AN: 6035

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000939 AC: 5 AN: 53226

Other (OTH) AF: 0.00 AC: 0 AN: 1504

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000907

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.000626 AC: 76

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.89	D
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.26
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.92
MPC		0.71
ClinPred		0.22	T
GERP RS		-1.2
Varity_R		0.81
gMVP		0.84
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs760024863; hg19: chrX-117892080;