5-150076052-G-C

Variant names:

• chr5-150076052-G-C
• rs17651965
• NM_001288705.3:c.889+1224C>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.889+1224C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,236 control chromosomes in the GnomAD database, including 7,642 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 0.24 (7642 hom., cov: 33)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1R	NM_001288705.3	c.889+1224C>G		intron_variant	Intron 5 of 20	ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1	c.889+1224C>G		intron_variant	Intron 5 of 20		NM_001288705.3	ENSP00000501699.1
CSF1R	ENST00000286301.7	c.889+1224C>G		intron_variant	Intron 6 of 21	1		ENSP00000286301.3
CSF1R	ENST00000543093.1	c.889+1224C>G		intron_variant	Intron 5 of 5	1		ENSP00000445282.1
CSF1R	ENST00000504875.5	n.889+1224C>G		intron_variant	Intron 5 of 19	1		ENSP00000422212.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36965 AN: 152118 Hom.: 7621 Cov.: 33

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.243 AC: 37025 AN: 152236 Hom.: 7642 Cov.: 33 AF XY: 0.240 AC XY: 17887 AN XY: 74426

African (AFR) AF: 0.545 AC: 22628 AN: 41504

American (AMR) AF: 0.159 AC: 2428 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2728 AN: 5176

South Asian (SAS) AF: 0.168 AC: 810 AN: 4828

European-Finnish (FIN) AF: 0.0595 AC: 632 AN: 10618

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6610 AN: 68020

Other (OTH) AF: 0.236 AC: 500 AN: 2116

Alfa AF: 0.175 Hom.: 564

Bravo AF: 0.266

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-0.14
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: rs17651965; hg19: chr5-149455615;