rs3918020

Variant names:

• chr1-36469807-C-A
• rs3918020
• NM_000760.4:c.1319G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-36469807-C-A
• chr1-36469807-C-G
• chr1-36469807-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000760.4(CSF3R):​c.1319G>T​(p.Arg440Leu) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R440Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF3R NM_000760.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000297367 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12398988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4	c.1319G>T	p.Arg440Leu	missense_variant	Exon 11 of 17	ENST00000373106.6	NP_000751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6	c.1319G>T	p.Arg440Leu	missense_variant	Exon 11 of 17	1	NM_000760.4	ENSP00000362198.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.83
DANN	Benign	0.84
DEOGEN2	Benign	0.16	T;.;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.64	.;.;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M
PhyloP100		-1.4
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.4	N;D;N;N;D
REVEL	Benign	0.096
Sift	Benign	0.063	T;T;T;T;T
Sift4G	Uncertain	0.057	T;T;T;T;T
Polyphen		0.68	P;P;P;P;P
Vest4		0.34
MutPred		0.41		Loss of MoRF binding (P = 0.0521);Loss of MoRF binding (P = 0.0521);Loss of MoRF binding (P = 0.0521);Loss of MoRF binding (P = 0.0521);Loss of MoRF binding (P = 0.0521);
MVP		0.35
MPC		0.37
ClinPred		0.17	T
GERP RS		-11
Varity_R		0.071
gMVP		0.48
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs3918020; hg19: chr1-36935408;