chrX-118727657-C-T

Variant names:

• chrX-118727657-C-T
• NM_001560.3:c.19C>T

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.19C>T​(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 804,995 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000016 (0 hom. 5 hem.)
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.949
• 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=0.18694648).
• BS2: High Hemizygotes in GnomAdExome4 at 5 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.19C>T	p.Leu7Phe	missense	Exon 1 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.19C>T	p.Leu7Phe	missense	Exon 1 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000371642.1	TSL:1	c.19C>T	p.Leu7Phe	missense	Exon 1 of 6	ENSP00000360705.1	P78552-2
	IL13RA1	ENST00000965042.1		c.19C>T	p.Leu7Phe	missense	Exon 1 of 12	ENSP00000635101.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000161 AC: 13 AN: 804995 Hom.: 0 Cov.: 23 AF XY: 0.0000204 AC XY: 5 AN XY: 244999

African (AFR) AF: 0.00 AC: 0 AN: 17567

American (AMR) AF: 0.00 AC: 0 AN: 6036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9688

East Asian (EAS) AF: 0.00 AC: 0 AN: 19202

South Asian (SAS) AF: 0.00 AC: 0 AN: 14293

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1997

European-Non Finnish (NFE) AF: 0.0000189 AC: 13 AN: 688197

Other (OTH) AF: 0.00 AC: 0 AN: 32101

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	0.083
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.95
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.021	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
Vest4		0.094
MutPred		0.19		Loss of helix (P = 0.079)
MVP		0.50
MPC		0.46
ClinPred		0.21	T
GERP RS		2.4
PromoterAI		-0.062	Neutral
Varity_R		0.21
gMVP		0.45
Mutation Taster		=91/9	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

hg19: chrX-117861620;