dbSNP rs141490008: CSF3:p.Leu24Phe (chr17-40015720-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_172219.3(CSF3):c.70C>T(p.Leu24Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,595,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CSF3
NM_172219.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709

Publications

1 publications found

Variant links:

Genes affected

CSF3 (HGNC:2438): (colony stimulating factor 3) This gene encodes a member of the IL-6 superfamily of cytokines. The encoded cytokine controls the production, differentiation, and function of granulocytes. Granulocytes are a type of white blood cell that are part of the innate immune response. A modified form of this protein is commonly administered to manage chemotherapy-induced neutropenia. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2020]

CSF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13311285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSF3	NM_172219.3	MANE Select	c.70C>T	p.Leu24Phe	missense	Exon 2 of 5	NP_757373.1	Q6FH65
CSF3	NM_000759.4		c.70C>T	p.Leu24Phe	missense	Exon 2 of 5	NP_000750.1	P09919-1
CSF3	NM_172220.3		c.70C>T	p.Leu24Phe	missense	Exon 2 of 4	NP_757374.2	P09919-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSF3	ENST00000394149.8	TSL:1 MANE Select	c.70C>T	p.Leu24Phe	missense	Exon 2 of 5	ENSP00000377705.4	P09919-2
CSF3	ENST00000225474.6	TSL:1	c.70C>T	p.Leu24Phe	missense	Exon 2 of 5	ENSP00000225474.2	P09919-1
CSF3	ENST00000331769.6	TSL:1	c.58C>T	p.Leu20Phe	missense	Exon 1 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000319

AC:

AN:

219490

AF XY:

0.0000337

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000624

AC:

AN:

1443256

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716178

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

33192

American (AMR)

AF:

0.00

AC:

AN:

42432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25672

East Asian (EAS)

AF:

0.00

AC:

AN:

39102

South Asian (SAS)

AF:

0.00

AC:

AN:

83598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5100

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102564

Other (OTH)

AF:

0.0000168

AC:

AN:

59570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.586

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.42

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.65

M_CAP

Benign

0.0081

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

PhyloP100

0.71

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

REVEL

Benign

0.025

Sift

Benign

0.046

Sift4G

Pathogenic

0.0

Polyphen

0.45

Vest4

0.24

MVP

0.43

MPC

0.38

ClinPred

0.028

GERP RS

3.1

PromoterAI

0.13

Neutral

(source)

Varity_R

0.058

gMVP

0.28

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over