X-118758239-C-T

Variant names:

• chrX-118758239-C-T
• rs148722500
• NM_001560.3:c.673C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001560.3(IL13RA1):​c.673C>T​(p.Arg225Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 886,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R225S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000068 (0 hom. 1 hem.)
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10951272).

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.673C>T	p.Arg225Cys	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.673C>T	p.Arg225Cys	missense	Exon 5 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000371642.1	TSL:1	c.673C>T	p.Arg225Cys	missense	Exon 5 of 6	ENSP00000360705.1	P78552-2
	IL13RA1	ENST00000965042.1		c.814C>T	p.Arg272Cys	missense	Exon 6 of 12	ENSP00000635101.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000593 AC: 1 AN: 168749 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000412

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: 0.00000677 AC: 6 AN: 886571 Hom.: 0 Cov.: 15 AF XY: 0.00000435 AC XY: 1 AN XY: 229775

African (AFR) AF: 0.0000443 AC: 1 AN: 22583

American (AMR) AF: 0.0000309 AC: 1 AN: 32376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16514

East Asian (EAS) AF: 0.00 AC: 0 AN: 28808

South Asian (SAS) AF: 0.00 AC: 0 AN: 40571

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37899

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3493

European-Non Finnish (NFE) AF: 0.00000600 AC: 4 AN: 666497

Other (OTH) AF: 0.00 AC: 0 AN: 37830

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.49
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.21
Sift	Benign	0.18	T
Sift4G	Benign	0.14	T
Polyphen		0.026	B
Vest4		0.18
MutPred		0.34		Loss of disorder (P = 0.0321)
MVP		0.53
MPC		0.24
ClinPred		0.19	T
GERP RS		0.30
Varity_R		0.12
gMVP		0.59
Mutation Taster		=94/6	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: rs148722500; hg19: chrX-117892202;