rs3829987

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001288705.3(CSF1R):c.889+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,674 control chromosomes in the GnomAD database, including 8,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 3060 hom., cov: 32)

Exomes 𝑓: 0.051 ( 5424 hom. )

Consequence

CSF1R
NM_001288705.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

Publications

13 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=-0.95).

BP6

Variant 5-150077248-G-A is Benign according to our data. Variant chr5-150077248-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239548.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.889+28C>T	intron	N/A	NP_001275634.1	P07333-1
CSF1R	NM_001349736.2		c.889+28C>T	intron	N/A	NP_001336665.1	P07333-1
CSF1R	NM_001375320.1		c.889+28C>T	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.889+28C>T	intron	N/A	ENSP00000501699.1	P07333-1
CSF1R	ENST00000286301.7	TSL:1	c.889+28C>T	intron	N/A	ENSP00000286301.3	P07333-1
CSF1R	ENST00000543093.1	TSL:1	c.889+28C>T	intron	N/A	ENSP00000445282.1	P07333-2

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21764

AN:

152010

Hom.:

3047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0533

Gnomad FIN

AF:

0.0478

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.145

GnomAD2 exomes

AF:

0.101

AC:

25309

AN:

251444

AF XY:

0.0861

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0502

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0757

GnomAD4 exome

AF:

0.0513

AC:

75025

AN:

1461546

Hom.:

5424

Cov.:

AF XY:

0.0494

AC XY:

35942

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.357

AC:

11933

AN:

33446

American (AMR)

AF:

0.240

AC:

10749

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0497

AC:

1298

AN:

26124

East Asian (EAS)

AF:

0.208

AC:

8243

AN:

39684

South Asian (SAS)

AF:

0.0449

AC:

3874

AN:

86228

European-Finnish (FIN)

AF:

0.0492

AC:

2627

AN:

53406

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5766

European-Non Finnish (NFE)

AF:

0.0280

AC:

31101

AN:

1111794

Other (OTH)

AF:

0.0758

AC:

4577

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

3441

6882

10324

13765

17206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1540

3080

4620

6160

7700

<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:

0.143

AC:

21824

AN:

152128

Hom.:

3060

Cov.:

AF XY:

0.144

AC XY:

10696

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.345

AC:

14322

AN:

41482

American (AMR)

AF:

0.198

AC:

3020

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3470

East Asian (EAS)

AF:

0.227

AC:

1169

AN:

5158

South Asian (SAS)

AF:

0.0533

AC:

257

AN:

4822

European-Finnish (FIN)

AF:

0.0478

AC:

507

AN:

10596

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2030

AN:

68004

Other (OTH)

AF:

0.147

AC:

311

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

780

1560

2340

3120

3900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.0902

Hom.:

2254

Bravo

AF:

0.166

Asia WGS

AF:

0.172

AC:

600

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

-0.95

CADD

Benign

0.070

(source)

DANN

Benign

0.45

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over