chr1-36480052-G-A

Variant names:

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

Variant summary

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

The NM_000760.4(CSF3R):​c.-20-536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 204,150 control chromosomes in the GnomAD database, including 12,931 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 0.33 (9243 hom., cov: 32)
  • Exomes 𝑓: 0.37 (3688 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

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>T		intron	N/A	NP_000751.1	Q99062-1
	CSF3R	NM_156039.3		c.-20-536C>T		intron	N/A	NP_724781.1	Q99062-3
	CSF3R	NM_172313.3		c.-20-536C>T		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>T		intron	N/A	ENSP00000362198.2	Q99062-1
	CSF3R	ENST00000373103.5	TSL:1	c.-20-536C>T		intron	N/A	ENSP00000362195.1	Q99062-3
	CSF3R	ENST00000373104.5	TSL:1	c.-20-536C>T		intron	N/A	ENSP00000362196.1	Q99062-4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50341 AN: 151982 Hom.: 9243 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.336

GnomAD4 exome AF: 0.365 AC: 19019 AN: 52050 Hom.: 3688 Cov.: 0 AF XY: 0.370 AC XY: 10133 AN XY: 27402

African (AFR) AF: 0.187 AC: 359 AN: 1918

American (AMR) AF: 0.479 AC: 1794 AN: 3742

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 437 AN: 1104

East Asian (EAS) AF: 0.0999 AC: 342 AN: 3422

South Asian (SAS) AF: 0.435 AC: 3407 AN: 7836

European-Finnish (FIN) AF: 0.383 AC: 627 AN: 1638

Middle Eastern (MID) AF: 0.399 AC: 55 AN: 138

European-Non Finnish (NFE) AF: 0.373 AC: 11108 AN: 29778

Other (OTH) AF: 0.360 AC: 890 AN: 2474

GnomAD4 genome AF: 0.331 AC: 50355 AN: 152100 Hom.: 9243 Cov.: 32 AF XY: 0.333 AC XY: 24797 AN XY: 74354

African (AFR) AF: 0.188 AC: 7788 AN: 41520

American (AMR) AF: 0.449 AC: 6858 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.119 AC: 617 AN: 5182

South Asian (SAS) AF: 0.445 AC: 2147 AN: 4828

European-Finnish (FIN) AF: 0.383 AC: 4045 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26335 AN: 67926

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.377 Hom.: 21875

Bravo AF: 0.325

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.69
PhyloP100		0.63
Mutation Taster		=99/1	polymorphism (auto)

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: rs3917924; hg19: chr1-36945653;