rs6645249

Variant names:

• chrX-1356997-A-G
• rs6645249
• NM_002183.4:c.732+661A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002183.4. 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
	IL3RA	NM_002183.4	MANE Select	c.732+661A>G		intron	N/A	NP_002174.1	P26951-1
	IL3RA	NM_001267713.2		c.498+661A>G		intron	N/A	NP_001254642.1	P26951-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL3RA	ENST00000331035.10	TSL:1 MANE Select	c.732+661A>G		intron	N/A	ENSP00000327890.4	P26951-1
	IL3RA	ENST00000964644.1		c.825+661A>G		intron	N/A	ENSP00000634703.1
	IL3RA	ENST00000903827.1		c.819+661A>G		intron	N/A	ENSP00000573886.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114803 AN: 151798 Hom.: 44204 Cov.: 32

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

African (AFR) AF: 0.873 AC: 36262 AN: 41522

American (AMR) AF: 0.730 AC: 11110 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2859 AN: 3466

East Asian (EAS) AF: 0.372 AC: 1917 AN: 5148

South Asian (SAS) AF: 0.690 AC: 3329 AN: 4824

European-Finnish (FIN) AF: 0.669 AC: 7038 AN: 10514

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.733 AC: 49759 AN: 67910

Other (OTH) AF: 0.750 AC: 1582 AN: 2108

Bravo AF: 0.769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.24
PhyloP100		-1.9

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: rs6645249; hg19: chrX-1475890;