Genetic Variant CSF1:p.Glu292Asp (chr1-109923497-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_000757.6(CSF1):c.876G>C(p.Glu292Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E292E) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CSF1
NM_000757.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.775

Publications

2 publications found

Variant links:

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]

CSF1 links:

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ACMG classification

Classification was made for transcript

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_000757.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSF1	NM_000757.6	MANE Select	c.876G>C	p.Glu292Asp	missense	Exon 6 of 9	NP_000748.4
CSF1	NM_172212.3		c.876G>C	p.Glu292Asp	missense	Exon 6 of 9	NP_757351.2	P09603-1
CSF1	NM_172210.3		c.876G>C	p.Glu292Asp	missense	Exon 6 of 9	NP_757349.2	P09603-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSF1	ENST00000329608.11	TSL:1 MANE Select	c.876G>C	p.Glu292Asp	missense	Exon 6 of 9	ENSP00000327513.6	P09603-1
CSF1	ENST00000369802.7	TSL:1	c.876G>C	p.Glu292Asp	missense	Exon 6 of 9	ENSP00000358817.3	P09603-1
CSF1	ENST00000369801.1	TSL:1	c.876G>C	p.Glu292Asp	missense	Exon 6 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251202

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111996

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.4

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Benign

-0.77

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.77

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

-0.78

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

REVEL

Benign

0.17

Sift

Uncertain

0.016

Sift4G

Uncertain

0.031

Polyphen

0.94

Vest4

0.069

MutPred

0.90

Gain of glycosylation at S297 (P = 0.3699)

MVP

0.37

MPC

0.12

ClinPred

0.13

GERP RS

-8.8

Varity_R

0.043

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over