chr5-132551553-C-T

Variant names:

• chr5-132551553-C-T
• rs2057687
• ENST00000638452.2:c.-168-7731C>T

Variant summary

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

The ENST00000638452.2(ENSG00000283782):​c.-168-7731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 139,976 control chromosomes in the GnomAD database, including 12,141 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 0.39 (12141 hom., cov: 31)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5	XM_005271988.5	c.42+5121G>A		intron_variant	Intron 1 of 4		XP_005272045.1
IL5	XM_011543373.4	c.-25+3603G>A		intron_variant	Intron 2 of 5		XP_011541675.1
IL5	XM_047417148.1	c.42+5121G>A		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.-168-7731C>T		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.393 AC: 55042 AN: 139884 Hom.: 12139 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.435

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.393 AC: 55042 AN: 139976 Hom.: 12141 Cov.: 31 AF XY: 0.395 AC XY: 27071 AN XY: 68490

African (AFR) AF: 0.155 AC: 4698 AN: 30280

American (AMR) AF: 0.491 AC: 7311 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1519 AN: 3458

East Asian (EAS) AF: 0.141 AC: 725 AN: 5152

South Asian (SAS) AF: 0.452 AC: 2170 AN: 4806

European-Finnish (FIN) AF: 0.454 AC: 4742 AN: 10440

Middle Eastern (MID) AF: 0.430 AC: 122 AN: 284

European-Non Finnish (NFE) AF: 0.481 AC: 32593 AN: 67718

Other (OTH) AF: 0.382 AC: 777 AN: 2032

Alfa AF: 0.390 Hom.: 1695

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs2057687; hg19: chr5-131887245;