dbSNP rs25645: CSF3:p.Leu182Leu (chr17-40016890-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_172219.3(CSF3):c.546G>A(p.Leu182Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,613,000 control chromosomes in the GnomAD database, including 115,584 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 0.30 ( 8303 hom., cov: 32)

Exomes 𝑓: 0.38 ( 107281 hom. )

Consequence

CSF3
NM_172219.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.648

Publications

49 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=0.648 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3	NM_172219.3 link	c.546G>A	p.Leu182Leu	synonymous_variant	Exon 5 of 5	ENST00000394149.8	NP_757373.1	P09919-2Q8N4W3Q6FH65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF3	ENST00000394149.8 link	c.546G>A	p.Leu182Leu	synonymous_variant	Exon 5 of 5	1	NM_172219.3	ENSP00000377705.4		P09919-2

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45921

AN:

151998

Hom.:

8313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0950

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.360

GnomAD2 exomes

AF:

0.391

AC:

97932

AN:

250438

AF XY:

0.399

show subpopulations

Gnomad AFR exome

AF:

0.0865

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.378

AC:

552651

AN:

1460884

Hom.:

107281

Cov.:

AF XY:

0.383

AC XY:

278071

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.0818

AC:

2739

AN:

33464

American (AMR)

AF:

0.488

AC:

21795

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

11065

AN:

26106

East Asian (EAS)

AF:

0.370

AC:

14690

AN:

39660

South Asian (SAS)

AF:

0.475

AC:

40909

AN:

86150

European-Finnish (FIN)

AF:

0.330

AC:

17580

AN:

53332

Middle Eastern (MID)

AF:

0.512

AC:

2787

AN:

5448

European-Non Finnish (NFE)

AF:

0.376

AC:

418432

AN:

1111748

Other (OTH)

AF:

0.375

AC:

22654

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

19474

38947

58421

77894

97368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13154

26308

39462

52616

65770

<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:

0.302

AC:

45904

AN:

152116

Hom.:

8303

Cov.:

AF XY:

0.303

AC XY:

22568

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0950

AC:

3947

AN:

41550

American (AMR)

AF:

0.397

AC:

6059

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1445

AN:

3470

East Asian (EAS)

AF:

0.415

AC:

2139

AN:

5154

South Asian (SAS)

AF:

0.463

AC:

2235

AN:

4826

European-Finnish (FIN)

AF:

0.323

AC:

3415

AN:

10586

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25462

AN:

67936

Other (OTH)

AF:

0.359

AC:

759

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1557

3115

4672

6230

7787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.354

Hom.:

19089

Bravo

AF:

0.301

Asia WGS

AF:

0.410

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.8

(source)

DANN

Benign

0.66

PhyloP100

0.65

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over