X-118773934-C-T

Variant names:

• chrX-118773934-C-T
• rs12853794
• NM_001560.3:c.1065C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001560.3(IL13RA1):​c.1065C>T​(p.Ile355Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,089,298 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. I355I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., 19 hem., cov: 23)
  • Exomes 𝑓: 0.000076 (0 hom. 21 hem.)
• Consequence: IL13RA1 NM_001560.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant X-118773934-C-T is Benign according to our data. Variant chrX-118773934-C-T is described in ClinVar as Benign. ClinVar VariationId is 727608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 19 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.1065C>T	p.Ile355Ile	synonymous	Exon 9 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.1065C>T	p.Ile355Ile	synonymous	Exon 9 of 11	ENSP00000360730.3	P78552-1
	IL13RA1	ENST00000965042.1		c.1206C>T	p.Ile402Ile	synonymous	Exon 10 of 12	ENSP00000635101.1
	IL13RA1	ENST00000865793.1		c.1065C>T	p.Ile355Ile	synonymous	Exon 9 of 12	ENSP00000535852.1

Frequencies

GnomAD3 genomes AF: 0.000620 AC: 69 AN: 111311 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000286

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: 0.000139 AC: 25 AN: 180120 AF XY: 0.0000927

Gnomad AFR exome AF: 0.00139

Gnomad AMR exome AF: 0.000150

Gnomad ASJ exome AF: 0.000269

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000757 AC: 74 AN: 977935 Hom.: 0 Cov.: 20 AF XY: 0.0000736 AC XY: 21 AN XY: 285265

African (AFR) AF: 0.00158 AC: 38 AN: 24098

American (AMR) AF: 0.000229 AC: 8 AN: 34915

Ashkenazi Jewish (ASJ) AF: 0.000270 AC: 5 AN: 18545

East Asian (EAS) AF: 0.00 AC: 0 AN: 29611

South Asian (SAS) AF: 0.0000194 AC: 1 AN: 51494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40395

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3886

European-Non Finnish (NFE) AF: 0.00000682 AC: 5 AN: 732820

Other (OTH) AF: 0.000403 AC: 17 AN: 42171

GnomAD4 genome AF: 0.000629 AC: 70 AN: 111363 Hom.: 0 Cov.: 23 AF XY: 0.000566 AC XY: 19 AN XY: 33543

African (AFR) AF: 0.00219 AC: 67 AN: 30637

American (AMR) AF: 0.000285 AC: 3 AN: 10517

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2665

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5881

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53064

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.000651 Hom.: 4

Bravo AF: 0.00107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.21
DANN	Benign	0.79
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12853794; hg19: chrX-117907897;