17-40017649-C-T

Position:

• chr17-40017649-C-T

Variant summary

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

The NM_172219.3(CSF3):​c.*690C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,010 control chromosomes in the GnomAD database, including 10,071 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 (10055 hom., cov: 30)
  • Exomes 𝑓: 0.38 (16 hom.)
• Consequence: CSF3 NM_172219.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3	NM_172219.3	c.*690C>T		3_prime_UTR_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.*690C>T		3_prime_UTR_variant	5/5	1	NM_172219.3	ENSP00000377705.4

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54933 AN: 151626 Hom.: 10038 Cov.: 30

Gnomad AFR AF: 0.315

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: 0.391

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.380 AC: 101 AN: 266 Hom.: 16 Cov.: 0 AF XY: 0.331 AC XY: 55 AN XY: 166

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.363 AC: 55013 AN: 151744 Hom.: 10055 Cov.: 30 AF XY: 0.360 AC XY: 26716 AN XY: 74148

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.343

Alfa AF: 0.349 Hom.: 4015

Bravo AF: 0.358

Asia WGS AF: 0.370 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.56

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: rs1042658; hg19: chr17-38173902;