chr5-132060983-A-G

Variant names:

• chr5-132060983-A-G
• rs35482671
• NM_000588.4:c.179A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000588.4(IL3):​c.179A>G​(p.Asn60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,614,044 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: IL3 NM_000588.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.24
• Publications: 13 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047552586).
• BP6: Variant 5-132060983-A-G is Benign according to our data. Variant chr5-132060983-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 720302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 284 AD gene.

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.179A>G	p.Asn60Ser	missense	Exon 2 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.179A>G	p.Asn60Ser	missense	Exon 2 of 5	ENSP00000296870.2
	ENSG00000303119	ENST00000791953.1		n.85+1657T>C		intron	N/A
	ENSG00000303119	ENST00000791954.1		n.248+488T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00169 AC: 425 AN: 251366 AF XY: 0.00174

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00284

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00301 AC: 4399 AN: 1461762 Hom.: 13 Cov.: 32 AF XY: 0.00289 AC XY: 2103 AN XY: 727192

African (AFR) AF: 0.000418 AC: 14 AN: 33474

American (AMR) AF: 0.00170 AC: 76 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86250

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00371 AC: 4122 AN: 1111906

Other (OTH) AF: 0.00235 AC: 142 AN: 60390

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74460

African (AFR) AF: 0.000746 AC: 31 AN: 41582

American (AMR) AF: 0.00203 AC: 31 AN: 15304

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00301 AC: 205 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00254 Hom.: 1

Bravo AF: 0.00240

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00163 AC: 198

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IL3: BP4, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.46
DANN	Benign	0.81
DEOGEN2	Benign	0.38	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.2
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.032
Sift	Uncertain	0.025	D
Sift4G	Benign	0.20	T
Polyphen		0.048	B
Vest4		0.033
MVP		0.11
MPC		0.23
ClinPred		0.0031	T
GERP RS		-5.8
PromoterAI		-0.058	Neutral
Varity_R		0.11
gMVP		0.39
Mutation Taster		=96/4	polymorphism

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: rs35482671; hg19: chr5-131396676;