X-118727657-C-T

Position:

• chrX-118727657-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18694648).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13RA1	NM_001560.3	c.19C>T	p.Leu7Phe	missense_variant	1/11	ENST00000371666.8	NP_001551.1
IL13RA1	XM_047442096.1	c.19C>T	p.Leu7Phe	missense_variant	1/11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL13RA1	ENST00000371666.8	c.19C>T	p.Leu7Phe	missense_variant	1/11	1	NM_001560.3	ENSP00000360730.3
IL13RA1	ENST00000371642.1	c.19C>T	p.Leu7Phe	missense_variant	1/6	1		ENSP00000360705.1
IL13RA1	ENST00000652600.1	c.-1+295C>T		intron_variant				ENSP00000498980.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.19C>T (p.L7F) alteration is located in exon 1 (coding exon 1) of the IL13RA1 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the leucine (L) at amino acid position 7 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.021	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0030	B;.
Vest4		0.094
MutPred		0.19		Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.50
MPC		0.46
ClinPred		0.21	T
GERP RS		2.4
Varity_R		0.21
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-117861620;