rs2069818

Variant names:

• chr5-132541832-G-T
• rs2069818
• NM_000879.3:c.384C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132541832-G-T
• chr5-132541832-G-A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000879.3(IL5):​c.384C>A​(p.Thr128Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,611,668 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (172 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (184 hom.)
• Consequence: IL5 NM_000879.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.96
• Publications: 17 publications found

Genes affected

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]

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 5-132541832-G-T is Benign according to our data. Variant chr5-132541832-G-T is described in ClinVar as Benign. ClinVar VariationId is 769306.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000879.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5	NM_000879.3	MANE Select	c.384C>A	p.Thr128Thr	synonymous	Exon 4 of 4	NP_000870.1	P05113-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL5	ENST00000231454.6	TSL:1 MANE Select	c.384C>A	p.Thr128Thr	synonymous	Exon 4 of 4	ENSP00000231454.1	P05113-1
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-168-17452G>T		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	IL5	ENST00000877569.1		c.384C>A	p.Thr128Thr	synonymous	Exon 5 of 5	ENSP00000547628.1

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4316 AN: 151894 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00756 AC: 1898 AN: 250990 AF XY: 0.00554

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00514

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000343

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00290 AC: 4240 AN: 1459656 Hom.: 184 Cov.: 29 AF XY: 0.00251 AC XY: 1825 AN XY: 726284

African (AFR) AF: 0.0991 AC: 3306 AN: 33374

American (AMR) AF: 0.00609 AC: 272 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000105 AC: 9 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5764

European-Non Finnish (NFE) AF: 0.000236 AC: 262 AN: 1110276

Other (OTH) AF: 0.00610 AC: 368 AN: 60322

GnomAD4 genome AF: 0.0285 AC: 4325 AN: 152012 Hom.: 172 Cov.: 32 AF XY: 0.0279 AC XY: 2070 AN XY: 74270

African (AFR) AF: 0.0971 AC: 4024 AN: 41440

American (AMR) AF: 0.0149 AC: 228 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 67990

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.00914 Hom.: 22

Bravo AF: 0.0337

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.47
PhyloP100		-5.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2069818; hg19: chr5-131877524;