rs6645249

Positions:

• chrX-1356997-A-G

Variant summary

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

The NM_002183.4(IL3RA):​c.732+661A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 151,916 control chromosomes in the GnomAD database, including 44,252 homozygotes. There are 55,619 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 0.76 (44252 hom., 55619 hem., cov: 32)
• Consequence: IL3RA NM_002183.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL3RA	NM_002183.4	c.732+661A>G		intron_variant		ENST00000331035.10
LOC101928032	XR_007068376.1	n.360-857T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL3RA	ENST00000331035.10	c.732+661A>G		intron_variant		1	NM_002183.4	P1
IL3RA	ENST00000381469.7	c.498+661A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114803 AN: 151798 Hom.: 44204 Cov.: 32 AF XY: 0.749 AC XY: 55510 AN XY: 74086

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.752

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.756 AC: 114911 AN: 151916 Hom.: 44252 Cov.: 32 AF XY: 0.749 AC XY: 55619 AN XY: 74214

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.750

Bravo AF: 0.769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.24

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

LitVar

Other links and lift over

dbSNP: rs6645249; hg19: chrX-1475890;