17-40015415-C-G

Variant names:

• chr17-40015415-C-G
• rs2227322
• ENST00000945857.1:c.-60C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000583218.5(CSF3):​c.-60C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,517,454 control chromosomes in the GnomAD database, including 108,585 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 0.36 (10094 hom., cov: 32)
  • Exomes 𝑓: 0.38 (98491 hom.)
• Consequence: CSF3 ENST00000583218.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 27 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	NM_172219.3	MANE Select	c.-60C>G		upstream_gene	N/A	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.-60C>G		upstream_gene	N/A	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.-60C>G		upstream_gene	N/A	NP_757374.2	P09919-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	ENST00000945857.1		c.-60C>G		5_prime_UTR	Exon 1 of 5	ENSP00000615916.1
	CSF3	ENST00000583218.5	TSL:2	c.-60C>G		5_prime_UTR	Exon 1 of 4	ENSP00000464421.1	J3QRX2
	CSF3	ENST00000394149.8	TSL:1 MANE Select	c.-60C>G		upstream_gene	N/A	ENSP00000377705.4	P09919-2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55078 AN: 151850 Hom.: 10077 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.378 AC: 515483 AN: 1365486 Hom.: 98491 Cov.: 31 AF XY: 0.374 AC XY: 251028 AN XY: 671798

African (AFR) AF: 0.311 AC: 9360 AN: 30138

American (AMR) AF: 0.336 AC: 9590 AN: 28510

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 7919 AN: 22966

East Asian (EAS) AF: 0.434 AC: 15383 AN: 35442

South Asian (SAS) AF: 0.264 AC: 19848 AN: 75274

European-Finnish (FIN) AF: 0.390 AC: 18464 AN: 47338

Middle Eastern (MID) AF: 0.262 AC: 1438 AN: 5490

European-Non Finnish (NFE) AF: 0.387 AC: 412046 AN: 1063956

Other (OTH) AF: 0.380 AC: 21435 AN: 56372

GnomAD4 genome AF: 0.363 AC: 55158 AN: 151968 Hom.: 10094 Cov.: 32 AF XY: 0.361 AC XY: 26804 AN XY: 74294

African (AFR) AF: 0.317 AC: 13138 AN: 41462

American (AMR) AF: 0.349 AC: 5323 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2276 AN: 5164

South Asian (SAS) AF: 0.259 AC: 1247 AN: 4822

European-Finnish (FIN) AF: 0.396 AC: 4183 AN: 10556

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26599 AN: 67924

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.385 Hom.: 1440

Bravo AF: 0.358

Asia WGS AF: 0.371 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		0.30
PromoterAI		-0.010	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2227322;

hg19: chr17-38171668;

COSMIC: COSV56642201;

COSMIC: COSV56642201;