Genetic Variant CSF3:c.-60C>G (chr17-40015415-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000583218.5(CSF3):c.-60C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,517,454 control chromosomes in the GnomAD database, including 108,585 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 0.36 ( 10094 hom., cov: 32)

Exomes 𝑓: 0.38 ( 98491 hom. )

Consequence

CSF3
ENST00000583218.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305

Publications

27 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=-0.51).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000583218.5. 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.-60C>G	upstream_gene	N/A	NP_757373.1
CSF3	NM_000759.4		c.-60C>G	upstream_gene	N/A	NP_000750.1
CSF3	NM_172220.3		c.-60C>G	upstream_gene	N/A	NP_757374.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CSF3	ENST00000583218.5	TSL:2	c.-60C>G	5_prime_UTR	Exon 1 of 4	ENSP00000464421.1
CSF3	ENST00000394149.8	TSL:1 MANE Select	c.-60C>G	upstream_gene	N/A	ENSP00000377705.4
CSF3	ENST00000225474.6	TSL:1	c.-60C>G	upstream_gene	N/A	ENSP00000225474.2

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55078

AN:

151850

Hom.:

10077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.339

GnomAD4 exome

AF:

0.378

AC:

515483

AN:

1365486

Hom.:

98491

Cov.:

AF XY:

0.374

AC XY:

251028

AN XY:

671798

show subpopulations

African (AFR)

AF:

0.311

AC:

9360

AN:

30138

American (AMR)

AF:

0.336

AC:

9590

AN:

28510

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

7919

AN:

22966

East Asian (EAS)

AF:

0.434

AC:

15383

AN:

35442

South Asian (SAS)

AF:

0.264

AC:

19848

AN:

75274

European-Finnish (FIN)

AF:

0.390

AC:

18464

AN:

47338

Middle Eastern (MID)

AF:

0.262

AC:

1438

AN:

5490

European-Non Finnish (NFE)

AF:

0.387

AC:

412046

AN:

1063956

Other (OTH)

AF:

0.380

AC:

21435

AN:

56372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

16934

33869

50803

67738

84672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13170

26340

39510

52680

65850

<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:

0.363

AC:

55158

AN:

151968

Hom.:

10094

Cov.:

AF XY:

0.361

AC XY:

26804

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.317

AC:

13138

AN:

41462

American (AMR)

AF:

0.349

AC:

5323

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1211

AN:

3468

East Asian (EAS)

AF:

0.441

AC:

2276

AN:

5164

South Asian (SAS)

AF:

0.259

AC:

1247

AN:

4822

European-Finnish (FIN)

AF:

0.396

AC:

4183

AN:

10556

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26599

AN:

67924

Other (OTH)

AF:

0.342

AC:

721

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1805

3611

5416

7222

9027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.385

Hom.:

1440

Bravo

AF:

0.358

Asia WGS

AF:

0.371

AC:

1287

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.30

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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