rs2069822

Positions:

• chr5-132543190-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000879.3(IL5):​c.145-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,504,580 control chromosomes in the GnomAD database, including 206 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 0.010 (15 hom., cov: 32)
  • Exomes 𝑓: 0.015 (191 hom.)
• Consequence: IL5 NM_000879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

Genes affected

IL5 (HGNC:6016): (interleukin 5) This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0101 (1532/152324) while in subpopulation NFE AF= 0.0162 (1100/68018). AF 95% confidence interval is 0.0154. There are 15 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL5	NM_000879.3	c.145-64A>G		intron_variant		ENST00000231454.6
IL5	XM_005271988.5	c.211-64A>G		intron_variant
IL5	XM_011543373.4	c.145-64A>G		intron_variant
IL5	XM_047417148.1	c.43-64A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL5	ENST00000231454.6	c.145-64A>G		intron_variant		1	NM_000879.3	P1
IL5	ENST00000462418.1	n.731A>G		non_coding_transcript_exon_variant	1/2	1
IL5	ENST00000450655.1	c.43-64A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1532 AN: 152206 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00883

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.0150 AC: 20241 AN: 1352256 Hom.: 191 Cov.: 20 AF XY: 0.0146 AC XY: 9874 AN XY: 678156

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.00489

Gnomad4 ASJ exome AF: 0.00728

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.0181

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0101 AC: 1532 AN: 152324 Hom.: 15 Cov.: 32 AF XY: 0.00988 AC XY: 736 AN XY: 74500

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.00882

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.0137 Hom.: 6

Bravo AF: 0.00935

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.061
DANN	Benign	0.73

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: rs2069822; hg19: chr5-131878882;