1-109923844-T-A

Position:

• chr1-109923844-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000757.6(CSF1):​c.1223T>A​(p.Leu408Gln) 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. 15/21 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. L408P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09804979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1	NM_000757.6	c.1223T>A	p.Leu408Gln	missense_variant	6/9	ENST00000329608.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11	c.1223T>A	p.Leu408Gln	missense_variant	6/9	1	NM_000757.6	P4
CSF1	ENST00000369802.7	c.1223T>A	p.Leu408Gln	missense_variant	6/9	1		P4
CSF1	ENST00000369801.1	c.1090+133T>A		intron_variant		1
CSF1	ENST00000420111.6	c.545-216T>A		intron_variant		5		A1

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	0.071
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.53
DANN	Benign	0.67
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.29	.;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.066
Sift	Benign	0.11	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.86	P;P
Vest4		0.15
MutPred		0.39		Loss of stability (P = 0.0523);Loss of stability (P = 0.0523);
MVP		0.17
MPC		0.12
ClinPred		0.15	T
GERP RS		-9.1
Varity_R		0.053
gMVP		0.23

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: rs1058885; hg19: chr1-110466466;