1-36467597-G-T

Variant names:

• chr1-36467597-G-T
• rs121918426
• NM_000760.4:c.1919C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000760.4(CSF3R):​c.1919C>A​(p.Thr640Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T640I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF3R NM_000760.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.234

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-36467597-G-T is Pathogenic according to our data. Variant chr1-36467597-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 16005.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4	c.1919C>A	p.Thr640Asn	missense_variant	Exon 15 of 17	ENST00000373106.6	NP_000751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6	c.1919C>A	p.Thr640Asn	missense_variant	Exon 15 of 17	1	NM_000760.4	ENSP00000362198.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary neutrophilia Pathogenic:1

Aug 03, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.6
DANN	Benign	0.90
DEOGEN2	Benign	0.21	T;.;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.53	.;.;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;L;L;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.071	T;T;T;T;T
Sift4G	Benign	0.078	T;T;T;T;T
Polyphen		0.0030	B;B;B;B;B
Vest4		0.74
MutPred		0.88		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.50
MPC		0.35
ClinPred		0.070	T
GERP RS		-0.53
Varity_R		0.088
gMVP		0.75

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: rs121918426; hg19: chr1-36933198; COSMIC: COSV58963377; COSMIC: COSV58963377;