5-132060785-C-T

Position:

• chr5-132060785-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

LOC105379174 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IL3	NM_000588.4	c.79C>T	p.Pro27Ser	missense_variant	1/5	ENST00000296870.3	NP_000579.2
LOC105379174	XR_001742531.2	n.211+686G>A		intron_variant, non_coding_transcript_variant
LOC105379174	XR_948784.3	n.398+686G>A		intron_variant, non_coding_transcript_variant
LOC105379174	XR_948785.3	n.228+686G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL3	ENST00000296870.3	c.79C>T	p.Pro27Ser	missense_variant	1/5	1	NM_000588.4	ENSP00000296870	P1

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

GnomAD3 exomes AF: 0.290 AC: 72991 AN: 251440 Hom.: 12035 AF XY: 0.281 AC XY: 38236 AN XY: 135902

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 SAS exome AF: 0.270

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

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.270

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

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.291

Alfa AF: 0.249 Hom.: 12952

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	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
MutationTaster	Benign	1.0	P
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
Varity_R		0.022
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs40401; hg19: chr5-131396478; COSMIC: COSV57308790;