rs6771148

Variant names:

• chr3-3101583-G-C
• rs6771148
• NM_175726.4:c.367+109C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-3101583-G-C
• chr3-3101583-G-T

Variant summary

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

The NM_175726.4(IL5RA):​c.367+109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,083,554 control chromosomes in the GnomAD database, including 328,581 homozygotes. 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 0.79 (48117 hom., cov: 33)
  • Exomes 𝑓: 0.77 (280464 hom.)
• Consequence: IL5RA NM_175726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 8 publications found

Genes affected

IL5RA (HGNC:6017): (interleukin 5 receptor subunit alpha) The protein encoded by this gene is an interleukin 5 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 IL5 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of IL5. This protein has been found to interact with syndecan binding protein (syntenin), which is required for IL5 mediated activation of the transcription factor SOX4. Several alternatively spliced transcript variants encoding four distinct isoforms have been reported. [provided by RefSeq, Jul 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5RA	NM_175726.4	c.367+109C>G		intron_variant	Intron 5 of 11	ENST00000446632.7	NP_783853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5RA	ENST00000446632.7	c.367+109C>G		intron_variant	Intron 5 of 11	5	NM_175726.4	ENSP00000412209.2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120734 AN: 152050 Hom.: 48059 Cov.: 33

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.807

GnomAD4 exome AF: 0.774 AC: 721235 AN: 931386 Hom.: 280464 AF XY: 0.778 AC XY: 367114 AN XY: 471812

African (AFR) AF: 0.835 AC: 18025 AN: 21592

American (AMR) AF: 0.853 AC: 22503 AN: 26372

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 14079 AN: 17432

East Asian (EAS) AF: 0.781 AC: 27390 AN: 35084

South Asian (SAS) AF: 0.900 AC: 52832 AN: 58678

European-Finnish (FIN) AF: 0.768 AC: 34423 AN: 44846

Middle Eastern (MID) AF: 0.814 AC: 2886 AN: 3544

European-Non Finnish (NFE) AF: 0.757 AC: 516036 AN: 681930

Other (OTH) AF: 0.789 AC: 33061 AN: 41908

GnomAD4 genome AF: 0.794 AC: 120852 AN: 152168 Hom.: 48117 Cov.: 33 AF XY: 0.797 AC XY: 59266 AN XY: 74384

African (AFR) AF: 0.833 AC: 34562 AN: 41488

American (AMR) AF: 0.828 AC: 12668 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2773 AN: 3472

East Asian (EAS) AF: 0.788 AC: 4082 AN: 5180

South Asian (SAS) AF: 0.897 AC: 4323 AN: 4820

European-Finnish (FIN) AF: 0.764 AC: 8088 AN: 10586

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51649 AN: 68006

Other (OTH) AF: 0.809 AC: 1708 AN: 2112

Alfa AF: 0.777 Hom.: 5752

Bravo AF: 0.799

Asia WGS AF: 0.864 AC: 3003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.38
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs6771148; hg19: chr3-3143267; COSMIC: COSV56525222; COSMIC: COSV56525222;