rs216137

Variant names:

• chr5-150056982-G-A
• rs216137
• NM_001288705.3:c.2319+305C>T

Variant summary

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

The NM_001288705.3(CSF1R):​c.2319+305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,916 control chromosomes in the GnomAD database, including 18,839 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 0.46 (18839 hom., cov: 30)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 9 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: 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	NM_001288705.3	MANE Select	c.2319+305C>T		intron	N/A	NP_001275634.1	P07333-1
	CSF1R	NM_001349736.2		c.2319+305C>T		intron	N/A	NP_001336665.1	P07333-1
	CSF1R	NM_001375320.1		c.2319+305C>T		intron	N/A	NP_001362249.1	P07333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.2319+305C>T		intron	N/A	ENSP00000501699.1	P07333-1
	CSF1R	ENST00000286301.7	TSL:1	c.2319+305C>T		intron	N/A	ENSP00000286301.3	P07333-1
	CSF1R	ENST00000504875.5	TSL:1	n.*140+305C>T		intron	N/A	ENSP00000422212.1	E9PEK4

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69906 AN: 151798 Hom.: 18842 Cov.: 30

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.460 AC: 69914 AN: 151916 Hom.: 18839 Cov.: 30 AF XY: 0.464 AC XY: 34416 AN XY: 74228

African (AFR) AF: 0.174 AC: 7200 AN: 41428

American (AMR) AF: 0.415 AC: 6324 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1973 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2309 AN: 5158

South Asian (SAS) AF: 0.520 AC: 2494 AN: 4796

European-Finnish (FIN) AF: 0.677 AC: 7156 AN: 10572

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40950 AN: 67930

Other (OTH) AF: 0.443 AC: 933 AN: 2104

Alfa AF: 0.562 Hom.: 19863

Bravo AF: 0.425

Asia WGS AF: 0.424 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.88
PhyloP100		-1.8
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: rs216137; hg19: chr5-149436545; COSMIC: COSV53831522; COSMIC: COSV53831522;