rs149810852

Variant names:

• chr1-109923252-C-T
• rs149810852
• NM_000757.6:c.631C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000757.6(CSF1):​c.631C>T​(p.Leu211Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,604,738 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.352
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014556259).
• BS2: High AC in GnomAd4 at 114 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.631C>T	p.Leu211Phe	missense	Exon 6 of 9	NP_000748.4
	CSF1	NM_172212.3		c.631C>T	p.Leu211Phe	missense	Exon 6 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.631C>T	p.Leu211Phe	missense	Exon 6 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.631C>T	p.Leu211Phe	missense	Exon 6 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.631C>T	p.Leu211Phe	missense	Exon 6 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.631C>T	p.Leu211Phe	missense	Exon 6 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000573 AC: 139 AN: 242532 AF XY: 0.000681

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000417

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.00104

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.00117 AC: 1701 AN: 1452440 Hom.: 3 Cov.: 30 AF XY: 0.00120 AC XY: 863 AN XY: 721794

African (AFR) AF: 0.000240 AC: 8 AN: 33292

American (AMR) AF: 0.000504 AC: 22 AN: 43672

Ashkenazi Jewish (ASJ) AF: 0.0000792 AC: 2 AN: 25268

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84550

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00145 AC: 1609 AN: 1107258

Other (OTH) AF: 0.000967 AC: 58 AN: 60006

GnomAD4 genome AF: 0.000749 AC: 114 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51 AN XY: 74472

African (AFR) AF: 0.000265 AC: 11 AN: 41566

American (AMR) AF: 0.00163 AC: 25 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68012

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00101 Hom.: 1

Bravo AF: 0.000975

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000675 AC: 82

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	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.35
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.045
Sift	Benign	0.16	T
Sift4G	Benign	0.11	T
Polyphen		0.059	B
Vest4		0.054
MVP		0.34
MPC		0.17
ClinPred		0.016	T
GERP RS		3.7
Varity_R		0.071
gMVP		0.12
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs149810852; hg19: chr1-110465874;