rs1654656504

Variant names:

• chr1-109911030-G-A
• rs1654656504
• NM_000757.6:c.7G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109911030-G-A
• chr1-109911030-G-C

Variant summary

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

The NM_000757.6(CSF1):​c.7G>A​(p.Ala3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 1,151,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600
• 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=0.3804291).

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.7G>A	p.Ala3Thr	missense	Exon 1 of 9	NP_000748.4
	CSF1	NM_172212.3		c.7G>A	p.Ala3Thr	missense	Exon 1 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.7G>A	p.Ala3Thr	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.7G>A	p.Ala3Thr	missense	Exon 1 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.7G>A	p.Ala3Thr	missense	Exon 1 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.7G>A	p.Ala3Thr	missense	Exon 1 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149668 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.98e-7 AC: 1 AN: 1001760 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 476190

African (AFR) AF: 0.00 AC: 0 AN: 19730

American (AMR) AF: 0.00 AC: 0 AN: 7714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10878

East Asian (EAS) AF: 0.00 AC: 0 AN: 17170

South Asian (SAS) AF: 0.00 AC: 0 AN: 21792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2476

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 869758

Other (OTH) AF: 0.00 AC: 0 AN: 37226

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149668 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 72970

African (AFR) AF: 0.00 AC: 0 AN: 41174

American (AMR) AF: 0.00 AC: 0 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9592

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

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67160

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.30
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.060
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.13
MutPred		0.61		Gain of glycosylation at A3 (P = 0.0017)
MVP		0.31
MPC		0.24
ClinPred		0.89	D
GERP RS		2.0
PromoterAI		-0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.19
Mutation Taster		=80/20	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: rs1654656504; hg19: chr1-110453652;