5-132075767-T-C

Variant names:

• chr5-132075767-T-C
• rs25882
• NM_000758.4:c.350T>C

Variant summary

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

The NM_000758.4(CSF2):​c.350T>C​(p.Ile117Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,607,090 control chromosomes in the GnomAD database, including 47,794 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 0.26 (5821 hom., cov: 33)
  • Exomes 𝑓: 0.23 (41973 hom.)
• Consequence: CSF2 NM_000758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 86 publications found

Genes affected

CSF2 (HGNC:2434): (colony stimulating factor 2) The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13. This gene plays a role in promoting tissue inflammation. Elevated levels of cytokines, including the one produced by this gene, have been detected in SARS-CoV-2 infected patients that develop acute respiratory distress syndrome. Mice deficient in this gene or its receptor develop pulmonary alveolar proteinosis. [provided by RefSeq, Aug 2020]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.9731318E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2	NM_000758.4	c.350T>C	p.Ile117Thr	missense_variant	Exon 4 of 4	ENST00000296871.4	NP_000749.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2	ENST00000296871.4	c.350T>C	p.Ile117Thr	missense_variant	Exon 4 of 4	1	NM_000758.4	ENSP00000296871.2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39826 AN: 152022 Hom.: 5817 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.265 AC: 65402 AN: 247098 AF XY: 0.258

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.228 AC: 331618 AN: 1454950 Hom.: 41973 Cov.: 31 AF XY: 0.228 AC XY: 164856 AN XY: 724190

African (AFR) AF: 0.309 AC: 10325 AN: 33402

American (AMR) AF: 0.243 AC: 10854 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7105 AN: 26108

East Asian (EAS) AF: 0.595 AC: 23591 AN: 39642

South Asian (SAS) AF: 0.235 AC: 20231 AN: 86192

European-Finnish (FIN) AF: 0.323 AC: 15854 AN: 49136

Middle Eastern (MID) AF: 0.248 AC: 1430 AN: 5758

European-Non Finnish (NFE) AF: 0.205 AC: 227346 AN: 1109746

Other (OTH) AF: 0.247 AC: 14882 AN: 60258

GnomAD4 genome AF: 0.262 AC: 39843 AN: 152140 Hom.: 5821 Cov.: 33 AF XY: 0.269 AC XY: 19975 AN XY: 74376

African (AFR) AF: 0.306 AC: 12693 AN: 41506

American (AMR) AF: 0.222 AC: 3394 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3163 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4822

European-Finnish (FIN) AF: 0.344 AC: 3634 AN: 10570

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13982 AN: 67996

Other (OTH) AF: 0.255 AC: 539 AN: 2112

Alfa AF: 0.231 Hom.: 14658

Bravo AF: 0.258

TwinsUK AF: 0.201 AC: 745

ALSPAC AF: 0.199 AC: 766

ESP6500AA AF: 0.319 AC: 1407

ESP6500EA AF: 0.212 AC: 1824

ExAC AF: 0.263 AC: 31920

Asia WGS AF: 0.445 AC: 1550 AN: 3478

EpiCase AF: 0.200

EpiControl AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.52
DANN	Benign	0.89
DEOGEN2	Benign	0.33	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.47
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.035
Sift	Benign	0.68	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.40
ClinPred		0.00059	T
GERP RS		-1.5
Varity_R		0.21
gMVP		0.054
Mutation Taster		=96/4	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: rs25882; hg19: chr5-131411460; COSMIC: COSV51522159; COSMIC: COSV51522159;