chr5-132075767-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000758.4(CSF2):ā€‹c.350T>Cā€‹(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. 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: š‘“ 0.26 ( 5821 hom., cov: 33)
Exomes š‘“: 0.23 ( 41973 hom. )

Consequence

CSF2
NM_000758.4 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.471
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
CSF2NM_000758.4 linkuse as main transcriptc.350T>C p.Ile117Thr missense_variant 4/4 ENST00000296871.4 NP_000749.2 P04141

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSF2ENST00000296871.4 linkuse as main transcriptc.350T>C p.Ile117Thr missense_variant 4/41 NM_000758.4 ENSP00000296871.2 P04141

Frequencies

GnomAD3 genomes
AF:
0.262
AC:
39826
AN:
152022
Hom.:
5817
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.265
AC:
65402
AN:
247098
Hom.:
10131
AF XY:
0.258
AC XY:
34537
AN XY:
133938
show subpopulations
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 SAS exome
AF:
0.236
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
show subpopulations
Gnomad4 AFR exome
AF:
0.309
Gnomad4 AMR exome
AF:
0.243
Gnomad4 ASJ exome
AF:
0.272
Gnomad4 EAS exome
AF:
0.595
Gnomad4 SAS exome
AF:
0.235
Gnomad4 FIN exome
AF:
0.323
Gnomad4 NFE exome
AF:
0.205
Gnomad4 OTH exome
AF:
0.247
GnomAD4 genome
AF:
0.262
AC:
39843
AN:
152140
Hom.:
5821
Cov.:
33
AF XY:
0.269
AC XY:
19975
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.306
Gnomad4 AMR
AF:
0.222
Gnomad4 ASJ
AF:
0.276
Gnomad4 EAS
AF:
0.612
Gnomad4 SAS
AF:
0.262
Gnomad4 FIN
AF:
0.344
Gnomad4 NFE
AF:
0.206
Gnomad4 OTH
AF:
0.255
Alfa
AF:
0.231
Hom.:
6917
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
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs25882; hg19: chr5-131411460; COSMIC: COSV51522159; COSMIC: COSV51522159; API