CSF1 p.Gly438Arg

Variant names:

• chr1-109923933-G-C
• NM_000757.6:c.1312G>C
• CSF1 p.Gly438Arg

Your query was ambiguous. Multiple possible variants found:

• chr1-109923933-G-C
• chr1-109923933-G-A
• chr1-109923933-GGG-CGT
• chr1-109923933-GGG-CGC
• chr1-109923933-GGG-CGA
• chr1-109923933-GGG-AGA

Variant summary

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

The NM_000757.6(CSF1):​c.1312G>C​(p.Gly438Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 0 publications found

Genes affected

CSF1 (HGNC:2432): (colony stimulating factor 1) The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. The encoded protein may be involved in development of the placenta. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

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=0.08122027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000757.6. 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
	CSF1	NM_000757.6	MANE Select	c.1312G>C	p.Gly438Arg	missense	Exon 6 of 9	NP_000748.4
	CSF1	NM_172212.3		c.1312G>C	p.Gly438Arg	missense	Exon 6 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.1091-127G>C		intron	N/A	NP_757349.2	P09603-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	ENST00000329608.11	TSL:1 MANE Select	c.1312G>C	p.Gly438Arg	missense	Exon 6 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.1312G>C	p.Gly438Arg	missense	Exon 6 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.1091-127G>C		intron	N/A	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.94
DANN	Benign	0.50
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.45
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.040
Sift	Benign	0.43	T
Sift4G	Benign	0.17	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-110466555;