NM_001560.3:c.883T>C

Variant names:

• chrX-118766850-T-C
• rs1340985667
• NM_001560.3:c.883T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001560.3(IL13RA1):​c.883T>C​(p.Ser295Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000957 in 1,044,676 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.0000043 (0 hom. 1 hem.)
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0890
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18053481).
• 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.883T>C	p.Ser295Pro	missense	Exon 8 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.883T>C	p.Ser295Pro	missense	Exon 8 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000965042.1		c.1024T>C	p.Ser342Pro	missense	Exon 9 of 12	ENSP00000635101.1
	IL13RA1	ENST00000865793.1		c.883T>C	p.Ser295Pro	missense	Exon 8 of 12	ENSP00000535852.1

Frequencies

GnomAD3 genomes AF: 0.0000535 AC: 6 AN: 112251 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000566

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000640 AC: 1 AN: 156338 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000495

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 4 AN: 932425 Hom.: 0 Cov.: 16 AF XY: 0.00000374 AC XY: 1 AN XY: 267363

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22474

American (AMR) AF: 0.000138 AC: 4 AN: 28945

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17223

East Asian (EAS) AF: 0.00 AC: 0 AN: 29248

South Asian (SAS) AF: 0.00 AC: 0 AN: 45440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40009

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3123

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 705785

Other (OTH) AF: 0.00 AC: 0 AN: 40178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000535 AC: 6 AN: 112251 Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2 AN XY: 34399

African (AFR) AF: 0.00 AC: 0 AN: 30887

American (AMR) AF: 0.000566 AC: 6 AN: 10602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3605

South Asian (SAS) AF: 0.00 AC: 0 AN: 2751

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53255

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.8
DANN	Benign	0.86
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.089
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Polyphen		0.63	P
Vest4		0.24
MutPred		0.57		Gain of catalytic residue at S295 (P = 0.0123)
MVP		0.56
MPC		0.27
ClinPred		0.059	T
GERP RS		1.4
Varity_R		0.70
gMVP		0.72
Mutation Taster		=67/33	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: rs1340985667; hg19: chrX-117900813;