NM_172219.3:c.*690C>G

Variant names:

• chr17-40017649-C-G
• rs1042658
• NM_172219.3:c.*690C>G

Variant summary

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

The NM_172219.3(CSF3):​c.*690C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,698 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: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: CSF3 NM_172219.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 32 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=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172219.3. 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.*690C>G		3_prime_UTR	Exon 5 of 5	NP_757373.1	Q6FH65
	CSF3	NM_000759.4		c.*690C>G		3_prime_UTR	Exon 5 of 5	NP_000750.1	P09919-1
	CSF3	NM_172220.3		c.*690C>G		3_prime_UTR	Exon 4 of 4	NP_757374.2	P09919-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3	ENST00000394149.8	TSL:1 MANE Select	c.*690C>G		3_prime_UTR	Exon 5 of 5	ENSP00000377705.4	P09919-2
	CSF3	ENST00000225474.6	TSL:1	c.*690C>G		3_prime_UTR	Exon 5 of 5	ENSP00000225474.2	P09919-1
	CSF3	ENST00000331769.6	TSL:1	c.*690C>G		3_prime_UTR	Exon 4 of 4	ENSP00000327766.2	Q8N4W3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151698 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151698 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74058

African (AFR) AF: 0.00 AC: 0 AN: 41256

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 6962

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.95
DANN	Benign	0.51
PhyloP100		-0.065

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

Other links and lift over

dbSNP: rs1042658; hg19: chr17-38173902;