17-40016314-A-G

Variant names:

• chr17-40016314-A-G
• rs749012642
• NM_172219.3:c.277A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_172219.3(CSF3):​c.277A>G​(p.Ser93Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,610,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CSF3 NM_172219.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00300
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24360701).

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.277A>G	p.Ser93Gly	missense	Exon 3 of 5	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.286A>G	p.Ser96Gly	missense	Exon 3 of 5	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.205-171A>G		intron	N/A	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.277A>G	p.Ser93Gly	missense	Exon 3 of 5	ENSP00000377705.4	P09919-2
	CSF3	ENST00000225474.6	TSL:1	c.286A>G	p.Ser96Gly	missense	Exon 3 of 5	ENSP00000225474.2	P09919-1
	CSF3	ENST00000331769.6	TSL:1	c.265A>G	p.Ser89Gly	missense	Exon 2 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151998 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000704 AC: 17 AN: 241454 AF XY: 0.0000610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000145 AC: 212 AN: 1458868 Hom.: 0 Cov.: 34 AF XY: 0.000123 AC XY: 89 AN XY: 725590

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 85912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.000186 AC: 207 AN: 1110676

Other (OTH) AF: 0.0000830 AC: 5 AN: 60252

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151998 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74226

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.7
DANN	Benign	0.80
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.0030
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.023
Sift	Benign	0.31	T
Sift4G	Benign	0.37	T
Polyphen		0.0080	B
Vest4		0.14
MutPred		0.41		Gain of glycosylation at S95 (P = 0.026)
MVP		0.38
MPC		0.31
ClinPred		0.039	T
GERP RS		3.0
Varity_R		0.20
gMVP		0.20
Mutation Taster		=97/3	polymorphism

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: rs749012642; hg19: chr17-38172567;