X-118770110-T-C

Variant names:

• chrX-118770110-T-C
• rs2248857
• NM_001560.3:c.1009+3134T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001560.3(IL13RA1):​c.1009+3134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 259,725 control chromosomes in the GnomAD database, including 7,235 homozygotes. There are 22,749 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (4294 hom., 9779 hem., cov: 23)
  • Exomes 𝑓: 0.23 (2941 hom. 12970 hem.)
• Consequence: IL13RA1 NM_001560.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• 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]

TMEM30BP1 (HGNC:55058): (TMEM30B pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA1	NM_001560.3	c.1009+3134T>C		intron_variant	Intron 8 of 10	ENST00000371666.8	NP_001551.1
TMEM30BP1		n.118770110T>C		intragenic_variant
IL13RA1	XM_047442096.1	c.1009+3134T>C		intron_variant	Intron 8 of 10		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13RA1	ENST00000371666.8	c.1009+3134T>C		intron_variant	Intron 8 of 10	1	NM_001560.3	ENSP00000360730.3
TMEM30BP1	ENST00000506969.1	n.315T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
IL13RA1	ENST00000652600.1	c.1003+3134T>C		intron_variant	Intron 9 of 11			ENSP00000498980.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 32390 AN: 111062 Hom.: 4294 Cov.: 23

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.0459

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.230 AC: 34238 AN: 148612 Hom.: 2941 Cov.: 0 AF XY: 0.243 AC XY: 12970 AN XY: 53432

African (AFR) AF: 0.489 AC: 2046 AN: 4184

American (AMR) AF: 0.438 AC: 3779 AN: 8623

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 796 AN: 3363

East Asian (EAS) AF: 0.442 AC: 2613 AN: 5916

South Asian (SAS) AF: 0.322 AC: 8170 AN: 25377

European-Finnish (FIN) AF: 0.194 AC: 1392 AN: 7193

Middle Eastern (MID) AF: 0.251 AC: 412 AN: 1644

European-Non Finnish (NFE) AF: 0.158 AC: 13432 AN: 84793

Other (OTH) AF: 0.213 AC: 1598 AN: 7519

GnomAD4 genome AF: 0.292 AC: 32413 AN: 111113 Hom.: 4294 Cov.: 23 AF XY: 0.293 AC XY: 9779 AN XY: 33389

African (AFR) AF: 0.483 AC: 14704 AN: 30442

American (AMR) AF: 0.419 AC: 4422 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 662 AN: 2643

East Asian (EAS) AF: 0.420 AC: 1461 AN: 3479

South Asian (SAS) AF: 0.322 AC: 862 AN: 2674

European-Finnish (FIN) AF: 0.197 AC: 1184 AN: 6004

Middle Eastern (MID) AF: 0.350 AC: 76 AN: 217

European-Non Finnish (NFE) AF: 0.161 AC: 8541 AN: 52898

Other (OTH) AF: 0.310 AC: 470 AN: 1514

Alfa AF: 0.107 Hom.: 513

Bravo AF: 0.325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.90
Mutation Taster		=298/2	polymorphism (auto)

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: rs2248857; hg19: chrX-117904073; COSMIC: COSV65424259; COSMIC: COSV65424259;