5-132553417-A-G

Position:

• chr5-132553417-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000640655.2(ENSG00000283782):​c.-168-5867A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,252 control chromosomes in the GnomAD database, including 66,425 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 0.93 (66425 hom., cov: 32)
• Consequence: ENSG00000283782 ENST00000640655.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

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

Verdict is Benign. Variant got -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 = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL5	XM_005271988.5	c.42+3257T>C		intron_variant			XP_005272045.1
IL5	XM_011543373.4	c.-25+1739T>C		intron_variant			XP_011541675.1
IL5	XM_047417148.1	c.42+3257T>C		intron_variant			XP_047273104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000640655.2	c.-168-5867A>G		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141229 AN: 152134 Hom.: 66386 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.988

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.928 AC: 141322 AN: 152252 Hom.: 66425 Cov.: 32 AF XY: 0.931 AC XY: 69271 AN XY: 74444

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.945

Alfa AF: 0.966 Hom.: 20285

Bravo AF: 0.916

Asia WGS AF: 0.976 AC: 3394 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	3.1
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2522406; hg19: chr5-131889109;