17-40015714-A-G

Variant names:

• chr17-40015714-A-G
• rs755462486
• NM_172219.3:c.64A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172219.3(CSF3):​c.64A>G​(p.Ser22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,438,402 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CSF3 NM_172219.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0920
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08139944).

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.64A>G	p.Ser22Gly	missense	Exon 2 of 5	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.64A>G	p.Ser22Gly	missense	Exon 2 of 5	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.64A>G	p.Ser22Gly	missense	Exon 2 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.64A>G	p.Ser22Gly	missense	Exon 2 of 5	ENSP00000377705.4	P09919-2
	CSF3	ENST00000225474.6	TSL:1	c.64A>G	p.Ser22Gly	missense	Exon 2 of 5	ENSP00000225474.2	P09919-1
	CSF3	ENST00000331769.6	TSL:1	c.52A>G	p.Ser18Gly	missense	Exon 1 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000457 AC: 1 AN: 218598 AF XY: 0.00000847

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: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1438402 Hom.: 0 Cov.: 33 AF XY: 0.00000281 AC XY: 2 AN XY: 712672

African (AFR) AF: 0.00 AC: 0 AN: 33080

American (AMR) AF: 0.00 AC: 0 AN: 42252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25572

East Asian (EAS) AF: 0.00 AC: 0 AN: 38946

South Asian (SAS) AF: 0.00 AC: 0 AN: 83480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5006

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1098828

Other (OTH) AF: 0.00 AC: 0 AN: 59260

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000825 AC: 1

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	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.092
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.020
Sift	Benign	0.42	T
Sift4G	Benign	0.26	T
Polyphen		0.012	B
Vest4		0.27
MutPred		0.44		Gain of loop (P = 0.0051)
MVP		0.39
MPC		0.31
ClinPred		0.028	T
GERP RS		1.7
PromoterAI		-0.063	Neutral
Varity_R		0.073
gMVP		0.25
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs755462486; hg19: chr17-38171967; COSMIC: COSV56640255; COSMIC: COSV56640255;