rs13188584

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001288705.3(CSF1R):c.592+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,591,254 control chromosomes in the GnomAD database, including 12,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1130 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11460 hom. )

Consequence

CSF1R
NM_001288705.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29

Publications

12 publications found

Variant links:

Genes affected

CSF1R (HGNC:2433): (colony stimulating factor 1 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most if not all of the biological effects of this cytokine. Ligand binding activates the receptor kinase through a process of oligomerization and transphosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. Mutations in this gene have been associated with a predisposition to myeloid malignancy. The first intron of this gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene oriented in the opposite direction. Alternative splicing results in multiple transcript variants. Expression of a splice variant from an LTR promoter has been found in Hodgkin lymphoma (HL), HL cell lines and anaplastic large cell lymphoma. [provided by RefSeq, Mar 2017]

CSF1R Gene-Disease associations (from GenCC):

hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics
brain abnormalities, neurodegeneration, and dysosteosclerosis
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
leukoencephalopathy, diffuse hereditary, with spheroids 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
early-onset calcifying leukoencephalopathy-skeletal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CSF1R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-150080011-C-T is Benign according to our data. Variant chr5-150080011-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253351.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288705.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSF1R	NM_001288705.3	MANE Select	c.592+41G>A	intron	N/A	NP_001275634.1	P07333-1
CSF1R	NM_001349736.2		c.592+41G>A	intron	N/A	NP_001336665.1	P07333-1
CSF1R	NM_001375320.1		c.592+41G>A	intron	N/A	NP_001362249.1	P07333-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSF1R	ENST00000675795.1	MANE Select	c.592+41G>A	intron	N/A	ENSP00000501699.1	P07333-1
CSF1R	ENST00000286301.7	TSL:1	c.592+41G>A	intron	N/A	ENSP00000286301.3	P07333-1
CSF1R	ENST00000543093.1	TSL:1	c.592+41G>A	intron	N/A	ENSP00000445282.1	P07333-2

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18352

AN:

152140

Hom.:

1130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.120

AC:

28481

AN:

237290

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.0748

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.124

AC:

178210

AN:

1438998

Hom.:

11460

Cov.:

AF XY:

0.124

AC XY:

88090

AN XY:

712218

show subpopulations

African (AFR)

AF:

0.127

AC:

4209

AN:

33230

American (AMR)

AF:

0.117

AC:

5136

AN:

44010

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3520

AN:

24916

East Asian (EAS)

AF:

0.120

AC:

4733

AN:

39348

South Asian (SAS)

AF:

0.130

AC:

10781

AN:

83028

European-Finnish (FIN)

AF:

0.0805

AC:

4099

AN:

50904

Middle Eastern (MID)

AF:

0.132

AC:

715

AN:

5410

European-Non Finnish (NFE)

AF:

0.125

AC:

136914

AN:

1098702

Other (OTH)

AF:

0.136

AC:

8103

AN:

59450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9068

18136

27205

36273

45341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5120

10240

15360

20480

25600

<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:

0.121

AC:

18356

AN:

152256

Hom.:

1130

Cov.:

AF XY:

0.120

AC XY:

8901

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.119

AC:

4948

AN:

41554

American (AMR)

AF:

0.130

AC:

1994

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

473

AN:

3472

East Asian (EAS)

AF:

0.139

AC:

718

AN:

5166

South Asian (SAS)

AF:

0.127

AC:

612

AN:

4822

European-Finnish (FIN)

AF:

0.0706

AC:

750

AN:

10620

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8421

AN:

68008

Other (OTH)

AF:

0.129

AC:

272

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

861

1723

2584

3446

4307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.124

Hom.:

992

Bravo

AF:

0.125

Asia WGS

AF:

0.152

AC:

526

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0070

(source)

DANN

Benign

0.75

PhyloP100

-1.3

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