1-109911058-C-G

Variant names:

• chr1-109911058-C-G
• rs987277680
• NM_000757.6:c.35C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000757.6(CSF1):​c.35C>G​(p.Pro12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 1,107,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1583344).
• BS2: High AC in GnomAd4 at 6 AD gene.

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.35C>G	p.Pro12Arg	missense	Exon 1 of 9	NP_000748.4
	CSF1	NM_172212.3		c.35C>G	p.Pro12Arg	missense	Exon 1 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.35C>G	p.Pro12Arg	missense	Exon 1 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.35C>G	p.Pro12Arg	missense	Exon 1 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.35C>G	p.Pro12Arg	missense	Exon 1 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.35C>G	p.Pro12Arg	missense	Exon 1 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes AF: 0.0000403 AC: 6 AN: 148852 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000486

GnomAD4 exome AF: 0.00000417 AC: 4 AN: 958752 Hom.: 0 Cov.: 30 AF XY: 0.00000883 AC XY: 4 AN XY: 453234

African (AFR) AF: 0.000161 AC: 3 AN: 18608

American (AMR) AF: 0.00 AC: 0 AN: 6080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9302

East Asian (EAS) AF: 0.00 AC: 0 AN: 12958

South Asian (SAS) AF: 0.00 AC: 0 AN: 20352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842786

Other (OTH) AF: 0.0000288 AC: 1 AN: 34726

GnomAD4 genome AF: 0.0000403 AC: 6 AN: 148852 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 2 AN XY: 72536

African (AFR) AF: 0.000122 AC: 5 AN: 41104

American (AMR) AF: 0.00 AC: 0 AN: 14982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66778

Other (OTH) AF: 0.000486 AC: 1 AN: 2056

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions

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	0.096
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.091
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
Polyphen		0.85	P
Vest4		0.24
MutPred		0.56		Loss of glycosylation at P12 (P = 0.0234)
MVP		0.21
MPC		0.43
ClinPred		0.39	T
GERP RS		2.9
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.087
gMVP		0.34
Mutation Taster		=92/8	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: rs987277680; hg19: chr1-110453680;