rs2069812

Variant names:

• chr5-132544224-A-G
• rs2069812
• ENST00000638452.2:c.-168-15060A>G

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-168-15060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,114 control chromosomes in the GnomAD database, including 26,057 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 0.54 (26057 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 78 publications found

Genes affected

ENSG00000283782 (HGNC:):

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5	XM_005271988.5	c.43-722T>C		intron_variant	Intron 1 of 4		XP_005272045.1
IL5	XM_011543373.4	c.-24-722T>C		intron_variant	Intron 2 of 5		XP_011541675.1
IL5	XM_047417148.1	c.43-1098T>C		intron_variant	Intron 1 of 3		XP_047273104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000638452.2	c.-168-15060A>G		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82331 AN: 151996 Hom.: 26051 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.541 AC: 82341 AN: 152114 Hom.: 26057 Cov.: 32 AF XY: 0.546 AC XY: 40607 AN XY: 74372

African (AFR) AF: 0.203 AC: 8435 AN: 41492

American (AMR) AF: 0.632 AC: 9655 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2250 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1646 AN: 5166

South Asian (SAS) AF: 0.678 AC: 3266 AN: 4816

European-Finnish (FIN) AF: 0.712 AC: 7538 AN: 10580

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47719 AN: 68000

Other (OTH) AF: 0.547 AC: 1156 AN: 2114

Alfa AF: 0.649 Hom.: 74952

Bravo AF: 0.511

Asia WGS AF: 0.489 AC: 1703 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	0.010
DANN	Benign	0.56
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2069812; hg19: chr5-131879916;