5-150078565-T-C

Variant names:

• chr5-150078565-T-C
• rs2569076
• NM_001288705.3:c.593-317A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288705.3(CSF1R):​c.593-317A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,198 control chromosomes in the GnomAD database, including 50,624 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 0.81 (50624 hom., cov: 33)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	NM_001288705.3	MANE Select	c.593-317A>G		intron	N/A	NP_001275634.1
	CSF1R	NM_001349736.2		c.593-317A>G		intron	N/A	NP_001336665.1
	CSF1R	NM_001375320.1		c.593-317A>G		intron	N/A	NP_001362249.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.593-317A>G		intron	N/A	ENSP00000501699.1
	CSF1R	ENST00000286301.7	TSL:1	c.593-317A>G		intron	N/A	ENSP00000286301.3
	CSF1R	ENST00000543093.1	TSL:1	c.593-317A>G		intron	N/A	ENSP00000445282.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123570 AN: 152080 Hom.: 50583 Cov.: 33

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.784

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.813 AC: 123664 AN: 152198 Hom.: 50624 Cov.: 33 AF XY: 0.816 AC XY: 60750 AN XY: 74408

African (AFR) AF: 0.924 AC: 38367 AN: 41544

American (AMR) AF: 0.785 AC: 12015 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2754 AN: 3472

East Asian (EAS) AF: 0.803 AC: 4149 AN: 5166

South Asian (SAS) AF: 0.777 AC: 3744 AN: 4816

European-Finnish (FIN) AF: 0.833 AC: 8830 AN: 10606

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 51365 AN: 67982

Other (OTH) AF: 0.781 AC: 1644 AN: 2106

Alfa AF: 0.807 Hom.: 6454

Bravo AF: 0.813

Asia WGS AF: 0.795 AC: 2768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2569076; hg19: chr5-149458128; COSMIC: COSV53831747; COSMIC: COSV53831747;