Genetic Variant CSF1:c.226-142C>T (chr1-109917151-C-T) – 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.226-142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 775,494 control chromosomes in the GnomAD database, including 47,357 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7262 hom., cov: 31)

Exomes 𝑓: 0.35 ( 40095 hom. )

Consequence

CSF1
NM_000757.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.500

Publications

3 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

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	Effect	Exon Rank	Protein
CSF1	NM_000757.6	MANE Select	c.226-142C>T	intron	N/A	NP_000748.4
CSF1	NM_172212.3		c.226-142C>T	intron	N/A	NP_757351.2
CSF1	NM_172210.3		c.226-142C>T	intron	N/A	NP_757349.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CSF1	ENST00000329608.11	TSL:1 MANE Select	c.226-142C>T	intron	N/A	ENSP00000327513.6
CSF1	ENST00000369802.7	TSL:1	c.226-142C>T	intron	N/A	ENSP00000358817.3
CSF1	ENST00000369801.1	TSL:1	c.226-142C>T	intron	N/A	ENSP00000358816.1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42888

AN:

151670

Hom.:

7258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0932

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.403

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.314

GnomAD4 exome

AF:

0.353

AC:

220114

AN:

623704

Hom.:

40095

AF XY:

0.356

AC XY:

116151

AN XY:

325934

show subpopulations

African (AFR)

AF:

0.0877

AC:

1421

AN:

16200

American (AMR)

AF:

0.421

AC:

10222

AN:

24268

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

6156

AN:

15160

East Asian (EAS)

AF:

0.390

AC:

13643

AN:

35010

South Asian (SAS)

AF:

0.425

AC:

22545

AN:

53022

European-Finnish (FIN)

AF:

0.285

AC:

11147

AN:

39154

Middle Eastern (MID)

AF:

0.327

AC:

782

AN:

2392

European-Non Finnish (NFE)

AF:

0.352

AC:

143274

AN:

406640

Other (OTH)

AF:

0.343

AC:

10924

AN:

31858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6929

13859

20788

27718

34647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2388

4776

7164

9552

11940

<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:

0.283

AC:

42904

AN:

151790

Hom.:

7262

Cov.:

AF XY:

0.284

AC XY:

21029

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.0930

AC:

3850

AN:

41414

American (AMR)

AF:

0.359

AC:

5485

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

1397

AN:

3470

East Asian (EAS)

AF:

0.407

AC:

2074

AN:

5102

South Asian (SAS)

AF:

0.443

AC:

2131

AN:

4806

European-Finnish (FIN)

AF:

0.273

AC:

2874

AN:

10532

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

23942

AN:

67888

Other (OTH)

AF:

0.321

AC:

676

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1458

2917

4375

5834

7292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.297

Hom.:

950

Bravo

AF:

0.282

Asia WGS

AF:

0.408

AC:

1417

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.7

(source)

DANN

Benign

0.61

PhyloP100

0.50

Mutation Taster

=100/0

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over