dbSNP rs2297706: CSF1:c.40-15C>A (chr1-109914244-C-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.40-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,585,488 control chromosomes in the GnomAD database, including 35,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.25 ( 5719 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29977 hom. )

Consequence

CSF1
NM_000757.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.284

Publications

11 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=-0.6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 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	UniProt
CSF1	NM_000757.6	MANE Select	c.40-15C>A	intron	N/A	NP_000748.4
CSF1	NM_172212.3		c.40-15C>A	intron	N/A	NP_757351.2	P09603-1
CSF1	NM_172210.3		c.40-15C>A	intron	N/A	NP_757349.2	P09603-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSF1	ENST00000329608.11	TSL:1 MANE Select	c.40-15C>A	intron	N/A	ENSP00000327513.6	P09603-1
CSF1	ENST00000369802.7	TSL:1	c.40-15C>A	intron	N/A	ENSP00000358817.3	P09603-1
CSF1	ENST00000369801.1	TSL:1	c.40-15C>A	intron	N/A	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37807

AN:

151908

Hom.:

5712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.220

AC:

51173

AN:

232522

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.190

AC:

272077

AN:

1433462

Hom.:

29977

Cov.:

AF XY:

0.189

AC XY:

134713

AN XY:

710938

show subpopulations

African (AFR)

AF:

0.400

AC:

13125

AN:

32806

American (AMR)

AF:

0.228

AC:

9415

AN:

41304

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

2956

AN:

24986

East Asian (EAS)

AF:

0.547

AC:

21197

AN:

38746

South Asian (SAS)

AF:

0.228

AC:

18311

AN:

80450

European-Finnish (FIN)

AF:

0.173

AC:

9170

AN:

52874

Middle Eastern (MID)

AF:

0.163

AC:

927

AN:

5684

European-Non Finnish (NFE)

AF:

0.169

AC:

185114

AN:

1097246

Other (OTH)

AF:

0.200

AC:

11862

AN:

59366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9534

19068

28602

38136

47670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7100

14200

21300

28400

35500

<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:

0.249

AC:

37849

AN:

152026

Hom.:

5719

Cov.:

AF XY:

0.252

AC XY:

18721

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.399

AC:

16506

AN:

41410

American (AMR)

AF:

0.226

AC:

3455

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

412

AN:

3470

East Asian (EAS)

AF:

0.532

AC:

2738

AN:

5148

South Asian (SAS)

AF:

0.229

AC:

1105

AN:

4822

European-Finnish (FIN)

AF:

0.171

AC:

1814

AN:

10600

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11125

AN:

67964

Other (OTH)

AF:

0.219

AC:

463

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1343

2686

4029

5372

6715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.140

Hom.:

444

Bravo

AF:

0.261

Asia WGS

AF:

0.378

AC:

1311

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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