Genetic Variant CSF3:c.196-181T>C (chr17-40016052-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_172219.3(CSF3):c.196-181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 851,806 control chromosomes in the GnomAD database, including 351,797 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.90 ( 61698 hom., cov: 30)

Exomes 𝑓: 0.91 ( 290099 hom. )

Consequence

CSF3
NM_172219.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

19 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

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	Effect	Exon Rank	Protein
CSF3	NM_172219.3	MANE Select	c.196-181T>C	intron	N/A	NP_757373.1
CSF3	NM_000759.4		c.205-181T>C	intron	N/A	NP_000750.1
CSF3	NM_172220.3		c.204+198T>C	intron	N/A	NP_757374.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CSF3	ENST00000394149.8	TSL:1 MANE Select	c.196-181T>C	intron	N/A	ENSP00000377705.4
CSF3	ENST00000225474.6	TSL:1	c.205-181T>C	intron	N/A	ENSP00000225474.2
CSF3	ENST00000331769.6	TSL:1	c.184-181T>C	intron	N/A	ENSP00000327766.2

Frequencies

GnomAD3 genomes

AF:

0.900

AC:

136764

AN:

151922

Hom.:

61645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.901

Gnomad ASJ

AF:

0.881

Gnomad EAS

AF:

0.864

Gnomad SAS

AF:

0.791

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.930

Gnomad OTH

AF:

0.907

GnomAD4 exome

AF:

0.909

AC:

636141

AN:

699766

Hom.:

290099

Cov.:

AF XY:

0.905

AC XY:

320028

AN XY:

353502

show subpopulations

African (AFR)

AF:

0.881

AC:

14834

AN:

16846

American (AMR)

AF:

0.911

AC:

17661

AN:

19384

Ashkenazi Jewish (ASJ)

AF:

0.880

AC:

13330

AN:

15148

East Asian (EAS)

AF:

0.800

AC:

25590

AN:

31998

South Asian (SAS)

AF:

0.809

AC:

40654

AN:

50226

European-Finnish (FIN)

AF:

0.872

AC:

29011

AN:

33254

Middle Eastern (MID)

AF:

0.902

AC:

2234

AN:

2478

European-Non Finnish (NFE)

AF:

0.930

AC:

462005

AN:

496532

Other (OTH)

AF:

0.909

AC:

30822

AN:

33900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3077

6155

9232

12310

15387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6906

13812

20718

27624

34530

<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:

0.900

AC:

136878

AN:

152040

Hom.:

61698

Cov.:

AF XY:

0.893

AC XY:

66382

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.879

AC:

36439

AN:

41458

American (AMR)

AF:

0.901

AC:

13768

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

3057

AN:

3468

East Asian (EAS)

AF:

0.864

AC:

4441

AN:

5142

South Asian (SAS)

AF:

0.791

AC:

3811

AN:

4816

European-Finnish (FIN)

AF:

0.866

AC:

9173

AN:

10596

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.930

AC:

63226

AN:

67960

Other (OTH)

AF:

0.908

AC:

1916

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

689

1378

2068

2757

3446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.918

Hom.:

107251

Bravo

AF:

0.906

Asia WGS

AF:

0.869

AC:

3023

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.2

(source)

DANN

Benign

0.35

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(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

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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