17-40016890-G-C

Variant names:

• chr17-40016890-G-C
• NM_172219.3:c.546G>C
• CSF3 p.Leu182Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_172219.3(CSF3):​c.546G>C​(p.Leu182Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CSF3 NM_172219.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.648 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	NM_172219.3	MANE Select	c.546G>C	p.Leu182Leu	synonymous	Exon 5 of 5	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.555G>C	p.Leu185Leu	synonymous	Exon 5 of 5	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.447G>C	p.Leu149Leu	synonymous	Exon 4 of 4	NP_757374.2	P09919-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	ENST00000394149.8	TSL:1 MANE Select	c.546G>C	p.Leu182Leu	synonymous	Exon 5 of 5	ENSP00000377705.4	P09919-2
	CSF3	ENST00000225474.6	TSL:1	c.555G>C	p.Leu185Leu	synonymous	Exon 5 of 5	ENSP00000225474.2	P09919-1
	CSF3	ENST00000331769.6	TSL:1	c.534G>C	p.Leu178Leu	synonymous	Exon 4 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-38173143;