rs25645

Positions:

• chr17-40016890-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_172219.3(CSF3):​c.546G>A​(p.Leu182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,613,000 control chromosomes in the GnomAD database, including 115,584 homozygotes. 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: 𝑓 0.30 (8303 hom., cov: 32)
  • Exomes 𝑓: 0.38 (107281 hom.)
• Consequence: CSF3 NM_172219.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.648 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3	NM_172219.3	c.546G>A	p.Leu182=	synonymous_variant	5/5	ENST00000394149.8	NP_757373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3	ENST00000394149.8	c.546G>A	p.Leu182=	synonymous_variant	5/5	1	NM_172219.3	ENSP00000377705	A2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45921 AN: 151998 Hom.: 8313 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.391 AC: 97932 AN: 250438 Hom.: 20473 AF XY: 0.399 AC XY: 54007 AN XY: 135428

Gnomad AFR exome AF: 0.0865

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.427

Gnomad EAS exome AF: 0.418

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.378 AC: 552651 AN: 1460884 Hom.: 107281 Cov.: 46 AF XY: 0.383 AC XY: 278071 AN XY: 726710

Gnomad4 AFR exome AF: 0.0818

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.302 AC: 45904 AN: 152116 Hom.: 8303 Cov.: 32 AF XY: 0.303 AC XY: 22568 AN XY: 74364

Gnomad4 AFR AF: 0.0950

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.359

Alfa AF: 0.372 Hom.: 14195

Bravo AF: 0.301

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs25645; hg19: chr17-38173143; COSMIC: COSV56642265; COSMIC: COSV56642265;