rs1981404365

Variant names:

• chr17-40016585-C-T
• rs1981404365
• NM_172219.3:c.404C>T

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.404C>T​(p.Thr135Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CSF3 NM_172219.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75
• 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=0.11343178).

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.404C>T	p.Thr135Ile	missense	Exon 4 of 5	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.413C>T	p.Thr138Ile	missense	Exon 4 of 5	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.305C>T	p.Thr102Ile	missense	Exon 3 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.404C>T	p.Thr135Ile	missense	Exon 4 of 5	ENSP00000377705.4	P09919-2
	CSF3	ENST00000225474.6	TSL:1	c.413C>T	p.Thr138Ile	missense	Exon 4 of 5	ENSP00000225474.2	P09919-1
	CSF3	ENST00000331769.6	TSL:1	c.392C>T	p.Thr131Ile	missense	Exon 3 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461870 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.11
DANN	Benign	0.91
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.7
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.0080
Sift	Benign	0.46	T
Sift4G	Benign	0.53	T
Polyphen		0.0010	B
Vest4		0.099
MutPred		0.42		Loss of disorder (P = 0.0873)
MVP		0.34
MPC		0.36
ClinPred		0.032	T
GERP RS		-2.8
Varity_R		0.097
gMVP		0.15
Mutation Taster		=86/14	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: rs1981404365; hg19: chr17-38172838;