X-1352245-G-T

Position:

• chrX-1352245-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002183.4(IL3RA):​c.431+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,032 control chromosomes in the GnomAD database, including 442,571 homozygotes. There are 589,482 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 0.77 (46058 hom., 57062 hem., cov: 34)
  • Exomes 𝑓: 0.73 (396513 hom. 532420 hem.)
• Consequence: IL3RA NM_002183.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

Genes affected

IL3RA (HGNC:6012): (interleukin 3 receptor subunit alpha) The protein encoded by this gene is an interleukin 3 specific subunit of a heterodimeric cytokine receptor. The receptor is comprised of a ligand specific alpha subunit and a signal transducing beta subunit shared by the receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2/GM-CSF), and interleukin 5 (IL5). The binding of this protein to IL3 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of IL3. This gene and the gene encoding the colony stimulating factor 2 receptor alpha chain (CSF2RA) form a cytokine receptor gene cluster in a X-Y pseudoautosomal region on chromosomes X or Y. Alternatively spliced transcript variants encoding distinct isoforms have been found. [provided by RefSeq, Jun 2012]

LOC101928032 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL3RA	NM_002183.4	c.431+13G>T		intron_variant		ENST00000331035.10	NP_002174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL3RA	ENST00000331035.10	c.431+13G>T		intron_variant		1	NM_002183.4	ENSP00000327890.4
IL3RA	ENST00000381469.7	c.197+13G>T		intron_variant		5		ENSP00000370878.2
IL3RA	ENST00000432757.6	c.197+13G>T		intron_variant		2		ENSP00000414867.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117344 AN: 152032 Hom.: 46021 Cov.: 34 AF XY: 0.768 AC XY: 56974 AN XY: 74212

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.767

GnomAD3 exomes AF: 0.729 AC: 182466 AN: 250178 Hom.: 67822 AF XY: 0.730 AC XY: 98777 AN XY: 135260

Gnomad AFR exome AF: 0.888

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.824

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.716

Gnomad FIN exome AF: 0.779

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.739

GnomAD4 exome AF: 0.733 AC: 1070941 AN: 1460882 Hom.: 396513 Cov.: 91 AF XY: 0.733 AC XY: 532420 AN XY: 726558

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.716

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.737

GnomAD4 genome AF: 0.772 AC: 117434 AN: 152150 Hom.: 46058 Cov.: 34 AF XY: 0.768 AC XY: 57062 AN XY: 74340

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.764

Bravo AF: 0.777

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6603272; hg19: chrX-1471138; COSMIC: COSV58429672;