NM_001560.3:c.258A>G

Variant names:

• chrX-118746983-A-G
• rs377169391
• NM_001560.3:c.258A>G

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.258A>G​(p.Ile86Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,182,352 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 67 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.00020 (0 hom. 66 hem.)
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08525708).
• BS2: High Hemizygotes in GnomAdExome4 at 66 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.258A>G	p.Ile86Met	missense	Exon 3 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.258A>G	p.Ile86Met	missense	Exon 3 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000371642.1	TSL:1	c.258A>G	p.Ile86Met	missense	Exon 3 of 6	ENSP00000360705.1	P78552-2
	IL13RA1	ENST00000965042.1		c.399A>G	p.Ile133Met	missense	Exon 4 of 12	ENSP00000635101.1

Frequencies

GnomAD3 genomes AF: 0.0000628 AC: 7 AN: 111458 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 21 AN: 180218 AF XY: 0.0000617

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: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.000197 AC: 211 AN: 1070894 Hom.: 0 Cov.: 23 AF XY: 0.000195 AC XY: 66 AN XY: 338278

African (AFR) AF: 0.0000387 AC: 1 AN: 25856

American (AMR) AF: 0.00 AC: 0 AN: 34921

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19180

East Asian (EAS) AF: 0.00 AC: 0 AN: 30065

South Asian (SAS) AF: 0.00 AC: 0 AN: 52961

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4053

European-Non Finnish (NFE) AF: 0.000254 AC: 208 AN: 818174

Other (OTH) AF: 0.0000442 AC: 2 AN: 45212

GnomAD4 genome AF: 0.0000628 AC: 7 AN: 111458 Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1 AN XY: 33610

African (AFR) AF: 0.00 AC: 0 AN: 30651

American (AMR) AF: 0.00 AC: 0 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2641

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5952

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

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 53149

Other (OTH) AF: 0.00 AC: 0 AN: 1497

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.0000659 AC: 8

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	0.063
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.14
Sift	Benign	0.24	T
Sift4G	Benign	0.067	T
Polyphen		0.0060	B
Vest4		0.098
MVP		0.49
MPC		0.17
ClinPred		0.017	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.21
Mutation Taster		=99/1	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: rs377169391; hg19: chrX-117880946;