17-40016052-T-C

Position:

• chr17-40016052-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172219.3(CSF3):​c.196-181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 851,806 control chromosomes in the GnomAD database, including 351,797 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 0.90 (61698 hom., cov: 30)
  • Exomes 𝑓: 0.91 (290099 hom.)
• Consequence: CSF3 NM_172219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

CSF3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3	NM_172219.3	c.196-181T>C		intron_variant		ENST00000394149.8	NP_757373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3	ENST00000394149.8	c.196-181T>C		intron_variant		1	NM_172219.3	ENSP00000377705.4

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136764 AN: 151922 Hom.: 61645 Cov.: 30

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.907

GnomAD4 exome AF: 0.909 AC: 636141 AN: 699766 Hom.: 290099 Cov.: 9 AF XY: 0.905 AC XY: 320028 AN XY: 353502

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.880

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.872

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.909

GnomAD4 genome AF: 0.900 AC: 136878 AN: 152040 Hom.: 61698 Cov.: 30 AF XY: 0.893 AC XY: 66382 AN XY: 74300

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.908

Alfa AF: 0.921 Hom.: 85065

Bravo AF: 0.906

Asia WGS AF: 0.869 AC: 3023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.35

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: rs2071369; hg19: chr17-38172305;