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:):

ENSG00000303119 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
IL3	NM_000588.4 link	c.79C>T	p.Pro27Ser	missense_variant	Exon 1 of 5	ENST00000296870.3	NP_000579.2
LOC105379174	XR_001742531.2 link	n.211+686G>A		intron_variant	Intron 2 of 4
LOC105379174	XR_948784.3 link	n.398+686G>A		intron_variant	Intron 2 of 2
LOC105379174	XR_948785.3 link	n.228+686G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL3	ENST00000296870.3 link	c.79C>T	p.Pro27Ser	missense_variant	Exon 1 of 5	1	NM_000588.4	ENSP00000296870.2

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 v4.3

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

Vest4

0.014

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over