chr17-40016890-G-A

Variant names:

• chr17-40016890-G-A
• rs25645
• NM_172219.3:c.546G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 49 publications found

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]

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	NM_172219.3	MANE Select	c.546G>A	p.Leu182Leu	synonymous	Exon 5 of 5	NP_757373.1
	CSF3	NM_000759.4		c.555G>A	p.Leu185Leu	synonymous	Exon 5 of 5	NP_000750.1
	CSF3	NM_172220.3		c.447G>A	p.Leu149Leu	synonymous	Exon 4 of 4	NP_757374.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	ENST00000394149.8	TSL:1 MANE Select	c.546G>A	p.Leu182Leu	synonymous	Exon 5 of 5	ENSP00000377705.4
	CSF3	ENST00000225474.6	TSL:1	c.555G>A	p.Leu185Leu	synonymous	Exon 5 of 5	ENSP00000225474.2
	CSF3	ENST00000331769.6	TSL:1	c.534G>A	p.Leu178Leu	synonymous	Exon 4 of 4	ENSP00000327766.2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45921 AN: 151998 Hom.: 8313 Cov.: 32

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

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.: 46 AF XY: 0.383 AC XY: 278071 AN XY: 726710

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

GnomAD4 genome AF: 0.302 AC: 45904 AN: 152116 Hom.: 8303 Cov.: 32 AF XY: 0.303 AC XY: 22568 AN XY: 74364

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		0.65
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs25645; hg19: chr17-38173143; COSMIC: COSV56642265; COSMIC: COSV56642265;