1-36480052-G-C

Variant names:

• chr1-36480052-G-C
• rs3917924
• NM_000760.4:c.-20-536C>G

Variant summary

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

The NM_000760.4(CSF3R):​c.-20-536C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSF3R NM_000760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 10 publications found

Genes affected

CSF3R (HGNC:2439): (colony stimulating factor 3 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 3, a cytokine that controls the production, differentiation, and function of granulocytes. The encoded protein, which is a member of the family of cytokine receptors, may also function in some cell surface adhesion or recognition processes. Alternatively spliced transcript variants have been described. Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia. [provided by RefSeq, Aug 2010]

CSF3R Gene-Disease associations (from GenCC):

• hereditary neutrophilia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• autosomal recessive severe congenital neutropenia due to CSF3R deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000297367 (HGNC:):

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_000760.4. 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
	CSF3R	NM_000760.4	MANE Select	c.-20-536C>G		intron	N/A	NP_000751.1	Q99062-1
	CSF3R	NM_156039.3		c.-20-536C>G		intron	N/A	NP_724781.1	Q99062-3
	CSF3R	NM_172313.3		c.-20-536C>G		intron	N/A	NP_758519.1	Q99062-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3R	ENST00000373106.6	TSL:1 MANE Select	c.-20-536C>G		intron	N/A	ENSP00000362198.2	Q99062-1
	CSF3R	ENST00000373103.5	TSL:1	c.-20-536C>G		intron	N/A	ENSP00000362195.1	Q99062-3
	CSF3R	ENST00000373104.5	TSL:1	c.-20-536C>G		intron	N/A	ENSP00000362196.1	Q99062-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 52362 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27574

African (AFR) AF: 0.00 AC: 0 AN: 1932

American (AMR) AF: 0.00 AC: 0 AN: 3758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1108

East Asian (EAS) AF: 0.00 AC: 0 AN: 3428

South Asian (SAS) AF: 0.00 AC: 0 AN: 7872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 29984

Other (OTH) AF: 0.00 AC: 0 AN: 2498

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.77
PhyloP100		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3917924; hg19: chr1-36945653;