17-40015415-C-T

Variant names:

• chr17-40015415-C-T
• rs2227322
• ENST00000583218.5:c.-60C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000583218.5(CSF3):​c.-60C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CSF3 ENST00000583218.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000583218.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	NM_172219.3	MANE Select	c.-60C>T		upstream_gene	N/A	NP_757373.1
	CSF3	NM_000759.4		c.-60C>T		upstream_gene	N/A	NP_000750.1
	CSF3	NM_172220.3		c.-60C>T		upstream_gene	N/A	NP_757374.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	ENST00000583218.5	TSL:2	c.-60C>T		5_prime_UTR	Exon 1 of 4	ENSP00000464421.1
	CSF3	ENST00000394149.8	TSL:1 MANE Select	c.-60C>T		upstream_gene	N/A	ENSP00000377705.4
	CSF3	ENST00000225474.6	TSL:1	c.-60C>T		upstream_gene	N/A	ENSP00000225474.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366184 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 672170

African (AFR) AF: 0.00 AC: 0 AN: 30158

American (AMR) AF: 0.00 AC: 0 AN: 28550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22980

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35450

South Asian (SAS) AF: 0.00 AC: 0 AN: 75318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064438

Other (OTH) AF: 0.00 AC: 0 AN: 56390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.30
PromoterAI		-0.065	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2227322; hg19: chr17-38171668;