ENST00000638452.2:c.-168-9736G>C

Variant names:

• chr5-132549548-G-C
• rs12652920
• ENST00000638452.2:c.-168-9736G>C

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-168-9736G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,138 control chromosomes in the GnomAD database, including 2,511 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 0.16 (2511 hom., cov: 33)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5	XM_005271988.5	c.43-6046C>G		intron_variant	Intron 1 of 4		XP_005272045.1
IL5	XM_011543373.4	c.-25+5608C>G		intron_variant	Intron 2 of 5		XP_011541675.1
IL5	XM_047417148.1	c.43-6422C>G		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.-168-9736G>C		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25056 AN: 152020 Hom.: 2508 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.165 AC: 25055 AN: 152138 Hom.: 2511 Cov.: 33 AF XY: 0.167 AC XY: 12403 AN XY: 74354

African (AFR) AF: 0.0512 AC: 2125 AN: 41544

American (AMR) AF: 0.145 AC: 2222 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 772 AN: 3470

East Asian (EAS) AF: 0.176 AC: 912 AN: 5184

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4816

European-Finnish (FIN) AF: 0.250 AC: 2635 AN: 10554

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14856 AN: 67964

Other (OTH) AF: 0.168 AC: 354 AN: 2108

Alfa AF: 0.207 Hom.: 455

Bravo AF: 0.148

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.54
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs12652920; hg19: chr5-131885240;