rs216148

Variant names:

• chr5-150066924-G-A
• rs216148
• NM_001288705.3:c.1626+1291C>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.1626+1291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,646 control chromosomes in the GnomAD database, including 6,050 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 0.23 (6043 hom., cov: 32)
  • Exomes 𝑓: 0.088 (7 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1R	NM_001288705.3	c.1626+1291C>T		intron_variant	Intron 10 of 20	ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1	c.1626+1291C>T		intron_variant	Intron 10 of 20		NM_001288705.3	ENSP00000501699.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34443 AN: 151798 Hom.: 6020 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.0877 AC: 64 AN: 730 Hom.: 7 AF XY: 0.0875 AC XY: 42 AN XY: 480

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AF: 0.214 AC: 3 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.286 AC: 4 AN: 14

South Asian (SAS) AF: 0.214 AC: 3 AN: 14

European-Finnish (FIN) AF: 0.0619 AC: 14 AN: 226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0746 AC: 30 AN: 402

Other (OTH) AF: 0.120 AC: 6 AN: 50

GnomAD4 genome AF: 0.227 AC: 34518 AN: 151916 Hom.: 6043 Cov.: 32 AF XY: 0.228 AC XY: 16916 AN XY: 74268

African (AFR) AF: 0.457 AC: 18907 AN: 41390

American (AMR) AF: 0.254 AC: 3889 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2398 AN: 5128

South Asian (SAS) AF: 0.228 AC: 1095 AN: 4798

European-Finnish (FIN) AF: 0.0575 AC: 609 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6452 AN: 67950

Other (OTH) AF: 0.214 AC: 451 AN: 2108

Alfa AF: 0.130 Hom.: 4086

Bravo AF: 0.252

Asia WGS AF: 0.356 AC: 1236 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-0.16
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: rs216148; hg19: chr5-149446487;