chr5-132060785-C-T

Variant names:

• chr5-132060785-C-T
• rs40401
• NM_000588.4:c.79C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.63
• Publications: 94 publications found

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]

ENSG00000303119 (HGNC:):

ACMG classification

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

Selected	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

Selected	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
	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.: 33

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

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.: 34 AF XY: 0.247 AC XY: 179873 AN XY: 727006

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

GnomAD4 genome AF: 0.331 AC: 50353 AN: 152116 Hom.: 9703 Cov.: 33 AF XY: 0.335 AC XY: 24870 AN XY: 74348

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: 61 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15416 AN: 68004

Other (OTH) AF: 0.291 AC: 616 AN: 2114

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	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0080
DANN	Benign	0.25
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.00023	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		-5.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.030
Sift	Benign	0.83	T
Sift4G	Benign	0.61	T
Polyphen		0.032	B
Vest4		0.014
MPC		0.23
ClinPred		0.0097	T
GERP RS		1.2
PromoterAI		-0.0044	Neutral
Varity_R		0.022
gMVP		0.57
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: rs40401; hg19: chr5-131396478; COSMIC: COSV57308790;