Genetic Variant NM_172219.3:c.*690C>T (chr17-40017649-C-T) – 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.*690C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,010 control chromosomes in the GnomAD database, including 10,071 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 ( 10055 hom., cov: 30)

Exomes 𝑓: 0.38 ( 16 hom. )

Consequence

CSF3
NM_172219.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0650

Publications

32 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=-0.81).

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: 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	UniProt
CSF3	NM_172219.3	MANE Select	c.*690C>T	3_prime_UTR	Exon 5 of 5	NP_757373.1	Q6FH65
CSF3	NM_000759.4		c.*690C>T	3_prime_UTR	Exon 5 of 5	NP_000750.1	P09919-1
CSF3	NM_172220.3		c.*690C>T	3_prime_UTR	Exon 4 of 4	NP_757374.2	P09919-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSF3	ENST00000394149.8	TSL:1 MANE Select	c.*690C>T	3_prime_UTR	Exon 5 of 5	ENSP00000377705.4	P09919-2
CSF3	ENST00000225474.6	TSL:1	c.*690C>T	3_prime_UTR	Exon 5 of 5	ENSP00000225474.2	P09919-1
CSF3	ENST00000331769.6	TSL:1	c.*690C>T	3_prime_UTR	Exon 4 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54933

AN:

151626

Hom.:

10038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

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:

0.391

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.380

AC:

101

AN:

266

Hom.:

Cov.:

AF XY:

0.331

AC XY:

AN XY:

166

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.415

AC:

AN:

130

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.136

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.380

AC:

AN:

Other (OTH)

AF:

0.438

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.363

AC:

55013

AN:

151744

Hom.:

10055

Cov.:

AF XY:

0.360

AC XY:

26716

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.316

AC:

13052

AN:

41348

American (AMR)

AF:

0.348

AC:

5325

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3472

East Asian (EAS)

AF:

0.441

AC:

2264

AN:

5132

South Asian (SAS)

AF:

0.259

AC:

1244

AN:

4808

European-Finnish (FIN)

AF:

0.396

AC:

4161

AN:

10508

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.391

AC:

26571

AN:

67886

Other (OTH)

AF:

0.343

AC:

723

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1733

3466

5199

6932

8665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.350

Hom.:

6962

Bravo

AF:

0.358

Asia WGS

AF:

0.370

AC:

1282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

(source)

DANN

Benign

0.56

PhyloP100

-0.065

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