X-118776517-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001560.3(IL13RA1):c.1191+6A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 672,886 control chromosomes in the GnomAD database, including 4 homozygotes. There are 184 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., 97 hem., cov: 21)
  • Exomes 𝑓: 0.00071 (2 hom. 87 hem.)
• Consequence: IL13RA1 NM_001560.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00002288
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.427

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-118776517-A-G is Benign according to our data. Variant chrX-118776517-A-G is described in ClinVar as [Benign]. Clinvar id is 780734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00495 (515/104058) while in subpopulation AFR AF= 0.0176 (483/27449). AF 95% confidence interval is 0.0163. There are 2 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL13RA1	NM_001560.3	c.1191+6A>G		splice_donor_region_variant, intron_variant		ENST00000371666.8
IL13RA1	XM_047442096.1	c.1191+6A>G		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL13RA1	ENST00000371666.8	c.1191+6A>G		splice_donor_region_variant, intron_variant		1	NM_001560.3	P1
IL13RA1	ENST00000652600.1	c.1185+6A>G		splice_donor_region_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 515 AN: 104042 Hom.: 2 Cov.: 21 AF XY: 0.00357 AC XY: 97 AN XY: 27160

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00180

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: 0.000174

Gnomad OTH AF: 0.00437

GnomAD3 exomes AF: 0.00181 AC: 273 AN: 151112 Hom.: 4 AF XY: 0.00108 AC XY: 51 AN XY: 47110

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000423

Gnomad OTH exome AF: 0.000282

GnomAD4 exome AF: 0.000710 AC: 404 AN: 568828 Hom.: 2 Cov.: 10 AF XY: 0.000542 AC XY: 87 AN XY: 160566

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.00116

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: 0.0000504

Gnomad4 OTH exome AF: 0.00143

GnomAD4 genome AF: 0.00495 AC: 515 AN: 104058 Hom.: 2 Cov.: 21 AF XY: 0.00357 AC XY: 97 AN XY: 27192

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.00180

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000174

Gnomad4 OTH AF: 0.00433

Alfa AF: 0.00425 Hom.: 17

Bravo AF: 0.00619

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.8
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0
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

LitVar

Other links and lift over

dbSNP: rs111349573; hg19: chrX-117910480;