Genetic Variant IL3:p.Pro27Ser (chr5-132060785-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000588.4(IL3):c.79C>T(p.Pro27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,492 control chromosomes in the GnomAD database, including 59,125 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9703 hom., cov: 33)

Exomes 𝑓: 0.25 ( 49422 hom. )

Consequence

IL3
NM_000588.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.63

Publications

94 publications found

Variant links:

Genes affected

IL3 (HGNC:6011): (interleukin 3) The protein encoded by this gene is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders. [provided by RefSeq, Jul 2008]

IL3 links:

ENSG00000303119 (HGNC:59130):

ENSG00000303119 links:

LOC105379174 (HGNC:):

LOC105379174 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2682548E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000588.4. 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
	IL3	NM_000588.4	MANE Select	c.79C>T	p.Pro27Ser	missense	Exon 1 of 5	NP_000579.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL3	ENST00000296870.3	TSL:1 MANE Select	c.79C>T	p.Pro27Ser	missense	Exon 1 of 5	ENSP00000296870.2	P08700
ENSG00000303119	ENST00000791953.1		n.85+1855G>A		intron	N/A
ENSG00000303119	ENST00000791954.1		n.248+686G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50273

AN:

151998

Hom.:

9679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.284

GnomAD2 exomes

AF:

0.290

AC:

72991

AN:

251440

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.531

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.248

AC:

361853

AN:

1461376

Hom.:

49422

Cov.:

AF XY:

0.247

AC XY:

179873

AN XY:

727006

show subpopulations

African (AFR)

AF:

0.540

AC:

18091

AN:

33476

American (AMR)

AF:

0.266

AC:

11890

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

8193

AN:

26134

East Asian (EAS)

AF:

0.537

AC:

21304

AN:

39694

South Asian (SAS)

AF:

0.267

AC:

23069

AN:

86250

European-Finnish (FIN)

AF:

0.323

AC:

17241

AN:

53410

Middle Eastern (MID)

AF:

0.213

AC:

1227

AN:

5750

European-Non Finnish (NFE)

AF:

0.220

AC:

244537

AN:

1111562

Other (OTH)

AF:

0.270

AC:

16301

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

14871

29743

44614

59486

74357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8766

17532

26298

35064

43830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.331

AC:

50353

AN:

152116

Hom.:

9703

Cov.:

AF XY:

0.335

AC XY:

24870

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.519

AC:

21512

AN:

41470

American (AMR)

AF:

0.257

AC:

3932

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1053

AN:

3470

East Asian (EAS)

AF:

0.542

AC:

2795

AN:

5156

South Asian (SAS)

AF:

0.290

AC:

1396

AN:

4820

European-Finnish (FIN)

AF:

0.323

AC:

3422

AN:

10580

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15416

AN:

68004

Other (OTH)

AF:

0.291

AC:

616

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1629

3258

4886

6515

8144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.263

Hom.:

20256

Bravo

AF:

0.336

TwinsUK

AF:

0.210

AC:

777

ALSPAC

AF:

0.219

AC:

844

ESP6500AA

AF:

0.515

AC:

2268

ESP6500EA

AF:

0.227

AC:

1951

ExAC

AF:

0.292

AC:

35409

Asia WGS

AF:

0.464

AC:

1614

AN:

3478

EpiCase

AF:

0.215

EpiControl

AF:

0.208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0080

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.35

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.30

MetaRNN

Benign

0.00023

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.81

PhyloP100

-5.6

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

REVEL

Benign

0.030

Sift

Benign

0.83

Sift4G

Benign

0.61

Polyphen

0.032

Vest4

0.014

MPC

0.23

ClinPred

0.0097

GERP RS

1.2

PromoterAI

-0.0044

Neutral

(source)

Varity_R

0.022

gMVP

0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over