1-109923716-C-G

Variant names:

• chr1-109923716-C-G
• rs333970
• NM_000757.6:c.1095C>G

Variant summary

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

The NM_172210.3(CSF1):​c.1090+5C>G variant causes a splice region, intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF1 NM_172210.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172210.3. 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.1095C>G	p.Thr365Thr	synonymous	Exon 6 of 9	NP_000748.4
	CSF1	NM_172212.3		c.1095C>G	p.Thr365Thr	synonymous	Exon 6 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.1090+5C>G		splice_region 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.1095C>G	p.Thr365Thr	synonymous	Exon 6 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.1095C>G	p.Thr365Thr	synonymous	Exon 6 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.1090+5C>G		splice_region intron	N/A	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.45
PhyloP100		-0.40
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -5

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

Other links and lift over

dbSNP: rs333970; hg19: chr1-110466338;