rs2228422

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001288705.3(CSF1R):c.726C>T(p.Thr242Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,613,634 control chromosomes in the GnomAD database, including 239,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18805 hom., cov: 31)

Exomes 𝑓: 0.54 ( 221004 hom. )

Consequence

CSF1R
NM_001288705.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0320

Publications

31 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: Ambry Genetics, Genomics England PanelApp, Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 5-150078115-G-A is Benign according to our data. Variant chr5-150078115-G-A is described in ClinVar as Benign. ClinVar VariationId is 352165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.032 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1R	NM_001288705.3 link	c.726C>T	p.Thr242Thr	synonymous_variant	Exon 4 of 21	ENST00000675795.1	NP_001275634.1	P07333-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1 link	c.726C>T	p.Thr242Thr	synonymous_variant	Exon 4 of 21		NM_001288705.3	ENSP00000501699.1		P07333-1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72739

AN:

151820

Hom.:

18804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.439

GnomAD2 exomes

AF:

0.510

AC:

128270

AN:

251364

AF XY:

0.519

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.697

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.543

AC:

794223

AN:

1461696

Hom.:

221004

Cov.:

AF XY:

0.545

AC XY:

396352

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.319

AC:

10686

AN:

33476

American (AMR)

AF:

0.415

AC:

18534

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

12820

AN:

26124

East Asian (EAS)

AF:

0.216

AC:

8585

AN:

39700

South Asian (SAS)

AF:

0.552

AC:

47637

AN:

86248

European-Finnish (FIN)

AF:

0.695

AC:

37124

AN:

53416

Middle Eastern (MID)

AF:

0.425

AC:

2453

AN:

5766

European-Non Finnish (NFE)

AF:

0.562

AC:

625297

AN:

1111870

Other (OTH)

AF:

0.515

AC:

31087

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19407

38814

58220

77627

97034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17204

34408

51612

68816

86020

<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:

0.479

AC:

72767

AN:

151938

Hom.:

18805

Cov.:

AF XY:

0.485

AC XY:

36054

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.321

AC:

13313

AN:

41432

American (AMR)

AF:

0.424

AC:

6478

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1720

AN:

3472

East Asian (EAS)

AF:

0.219

AC:

1127

AN:

5148

South Asian (SAS)

AF:

0.553

AC:

2661

AN:

4816

European-Finnish (FIN)

AF:

0.706

AC:

7466

AN:

10574

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38526

AN:

67900

Other (OTH)

AF:

0.437

AC:

923

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1812

3624

5437

7249

9061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.519

Hom.:

33258

Bravo

AF:

0.447

Asia WGS

AF:

0.414

AC:

1439

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary diffuse leukoencephalopathy with spheroids

Benign:4

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 09, 2015

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Brain abnormalities, neurodegeneration, and dysosteosclerosis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.3

(source)

DANN

Benign

0.39

PhyloP100

0.032

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over