NM_000757.6:c.1223T>G

Variant names:

• chr1-109923844-T-G
• rs1058885
• NM_000757.6:c.1223T>G

Variant summary

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

The NM_000757.6(CSF1):​c.1223T>G​(p.Leu408Arg) 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: 33)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 43 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: 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 (MetaRNN=0.05079487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.1223T>G	p.Leu408Arg	missense_variant	Exon 6 of 9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.1223T>G	p.Leu408Arg	missense_variant	Exon 6 of 9	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.052
DANN	Benign	0.46
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.27	.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.97	L;L
PhyloP100		-2.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.0080
Sift	Benign	0.15	T;T
Sift4G	Benign	0.83	T;T
Polyphen		0.0060	B;B
Vest4		0.12
MutPred		0.42		Gain of MoRF binding (P = 0.0251);Gain of MoRF binding (P = 0.0251);
MVP		0.10
MPC		0.17
ClinPred		0.069	T
GERP RS		-9.1
Varity_R		0.061
gMVP		0.21
Mutation Taster		=96/4	polymorphism

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: rs1058885; hg19: chr1-110466466;