5-132544224-A-G

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-168-15060A>G		intron	N/A	ENSP00000492349.2
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-310-12108A>G		intron	N/A	ENSP00000491158.2
	ENSG00000283782	ENST00000640655.2	TSL:5	c.-168-15060A>G		intron	N/A	ENSP00000491596.2

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 v4.9

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;