NM_172219.3:c.504G>T

Variant names:

• chr17-40016848-G-T
• rs9282660
• NM_172219.3:c.504G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_172219.3(CSF3):​c.504G>T​(p.Pro168Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,613,386 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (107 hom.)
• Consequence: CSF3 NM_172219.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.29
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-40016848-G-T is Benign according to our data. Variant chr17-40016848-G-T is described in ClinVar as Benign. ClinVar VariationId is 768877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	NM_172219.3	MANE Select	c.504G>T	p.Pro168Pro	synonymous	Exon 5 of 5	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.513G>T	p.Pro171Pro	synonymous	Exon 5 of 5	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.405G>T	p.Pro135Pro	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.504G>T	p.Pro168Pro	synonymous	Exon 5 of 5	ENSP00000377705.4	P09919-2
	CSF3	ENST00000225474.6	TSL:1	c.513G>T	p.Pro171Pro	synonymous	Exon 5 of 5	ENSP00000225474.2	P09919-1
	CSF3	ENST00000331769.6	TSL:1	c.492G>T	p.Pro164Pro	synonymous	Exon 4 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2759 AN: 152188 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00721 AC: 1811 AN: 251164 AF XY: 0.00640

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.00602

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00216

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.00373 AC: 5445 AN: 1461080 Hom.: 107 Cov.: 36 AF XY: 0.00364 AC XY: 2644 AN XY: 726844

African (AFR) AF: 0.0577 AC: 1930 AN: 33452

American (AMR) AF: 0.00651 AC: 291 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 604 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00542 AC: 467 AN: 86210

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53382

Middle Eastern (MID) AF: 0.0559 AC: 290 AN: 5186

European-Non Finnish (NFE) AF: 0.00121 AC: 1344 AN: 1111996

Other (OTH) AF: 0.00859 AC: 518 AN: 60308

GnomAD4 genome AF: 0.0181 AC: 2764 AN: 152306 Hom.: 64 Cov.: 33 AF XY: 0.0179 AC XY: 1330 AN XY: 74488

African (AFR) AF: 0.0558 AC: 2320 AN: 41568

American (AMR) AF: 0.00791 AC: 121 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 68020

Other (OTH) AF: 0.0199 AC: 42 AN: 2110

Alfa AF: 0.0109 Hom.: 12

Bravo AF: 0.0207

EpiCase AF: 0.00420

EpiControl AF: 0.00326

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.044
DANN	Benign	0.66
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs9282660; hg19: chr17-38173101;