Genetic Variant NM_000757.6:c.1312G>A (chr1-109923933-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000757.6(CSF1):c.1312G>A(p.Gly438Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,168 control chromosomes in the GnomAD database, including 2,236 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.059 ( 541 hom., cov: 34)

Exomes 𝑓: 0.023 ( 1695 hom. )

Consequence

CSF1
NM_000757.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

Publications

18 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017989278).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6 link	c.1312G>A	p.Gly438Arg	missense_variant	Exon 6 of 9	ENST00000329608.11	NP_000748.4	P09603-1A0A024R0A1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSF1	ENST00000329608.11 link	c.1312G>A	p.Gly438Arg	missense_variant	Exon 6 of 9	1	NM_000757.6	ENSP00000327513.6	P09603-1
CSF1	ENST00000369802.7 link	c.1312G>A	p.Gly438Arg	missense_variant	Exon 6 of 9	1		ENSP00000358817.3	P09603-1
CSF1	ENST00000369801.1 link	c.1091-127G>A		intron_variant	Intron 6 of 8	1		ENSP00000358816.1	P09603-2
CSF1	ENST00000420111.6 link	c.545-127G>A		intron_variant	Intron 5 of 8	5		ENSP00000407317.2	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8995

AN:

152224

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0754

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.0984

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.0535

GnomAD2 exomes

AF:

0.0496

AC:

12449

AN:

251096

AF XY:

0.0469

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0919

Gnomad ASJ exome

AF:

0.00726

Gnomad EAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.00758

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0231

AC:

33825

AN:

1461826

Hom.:

1695

Cov.:

AF XY:

0.0244

AC XY:

17744

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.148

AC:

4948

AN:

33480

American (AMR)

AF:

0.0901

AC:

4031

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00719

AC:

188

AN:

26136

East Asian (EAS)

AF:

0.168

AC:

6664

AN:

39700

South Asian (SAS)

AF:

0.0920

AC:

7938

AN:

86256

European-Finnish (FIN)

AF:

0.00818

AC:

437

AN:

53412

Middle Eastern (MID)

AF:

0.0182

AC:

105

AN:

5766

European-Non Finnish (NFE)

AF:

0.00678

AC:

7544

AN:

1111966

Other (OTH)

AF:

0.0326

AC:

1970

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

2226

4453

6679

8906

11132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

578

1156

1734

2312

2890

<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

AF:

0.0592

AC:

9021

AN:

152342

Hom.:

541

Cov.:

AF XY:

0.0607

AC XY:

4518

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.142

AC:

5888

AN:

41572

American (AMR)

AF:

0.0756

AC:

1157

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.150

AC:

777

AN:

5176

South Asian (SAS)

AF:

0.0985

AC:

476

AN:

4834

European-Finnish (FIN)

AF:

0.00706

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00723

AC:

492

AN:

68028

Other (OTH)

AF:

0.0539

AC:

114

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

419

839

1258

1678

2097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0283

Hom.:

714

Bravo

AF:

0.0685

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.141

AC:

622

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.0502

AC:

6097

Asia WGS

AF:

0.124

AC:

429

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.68

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

L;L

PhyloP100

-0.45

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.044

Sift

Benign

0.43

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.046

B;B

Vest4

0.058

MutPred

0.37

Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);

MPC

0.14

ClinPred

0.00083

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over