chr1-109917407-G-A

Variant names:

• chr1-109917407-G-A
• NM_000757.6:c.340G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000757.6(CSF1):​c.340G>A​(p.Glu114Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37006304).

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.340G>A	p.Glu114Lys	missense	Exon 4 of 9	NP_000748.4
	CSF1	NM_172212.3		c.340G>A	p.Glu114Lys	missense	Exon 4 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.340G>A	p.Glu114Lys	missense	Exon 4 of 9	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.340G>A	p.Glu114Lys	missense	Exon 4 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.340G>A	p.Glu114Lys	missense	Exon 4 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.340G>A	p.Glu114Lys	missense	Exon 4 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.44
MutPred		0.74		Gain of MoRF binding (P = 0.0201)
MVP		0.50
MPC		0.53
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.33
gMVP		0.38
Mutation Taster		=76/24	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

hg19: chr1-110460029;