rs6865659

Variant names:

• chr5-150106209-A-G
• rs6865659
• ENST00000286301.7:c.-181+7052T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-150106209-A-G
• chr5-150106209-A-T

Variant summary

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

The NM_005211.4(CSF1R):​c.-181+7052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,158 control chromosomes in the GnomAD database, including 6,747 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 0.29 (6747 hom., cov: 32)
• Consequence: CSF1R NM_005211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005211.4. 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_001375320.1		c.-286+7052T>C		intron	N/A	NP_001362249.1
	CSF1R	NM_005211.4		c.-181+7052T>C		intron	N/A	NP_005202.2
	CSF1R	NM_001375321.1		c.-396+7052T>C		intron	N/A	NP_001362250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000286301.7	TSL:1	c.-181+7052T>C		intron	N/A	ENSP00000286301.3
	CSF1R	ENST00000511344.1	TSL:4	c.-396+7052T>C		intron	N/A	ENSP00000421174.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44861 AN: 152040 Hom.: 6748 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.295 AC: 44876 AN: 152158 Hom.: 6747 Cov.: 32 AF XY: 0.290 AC XY: 21588 AN XY: 74392

African (AFR) AF: 0.270 AC: 11197 AN: 41486

American (AMR) AF: 0.268 AC: 4101 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2048 AN: 5176

South Asian (SAS) AF: 0.313 AC: 1508 AN: 4822

European-Finnish (FIN) AF: 0.182 AC: 1934 AN: 10604

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21895 AN: 67984

Other (OTH) AF: 0.322 AC: 680 AN: 2112

Alfa AF: 0.313 Hom.: 6161

Bravo AF: 0.298

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.62
PhyloP100		0.47
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: rs6865659; hg19: chr5-149485772;