5-150068065-A-G

Variant names:

• chr5-150068065-A-G
• rs216150
• NM_001288705.3:c.1626+150T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001288705.3(CSF1R):​c.1626+150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 618,964 control chromosomes in the GnomAD database, including 131,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33702 hom., cov: 31)
  • Exomes 𝑓: 0.64 (97894 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.638
• 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: Genomics England PanelApp, Ambry Genetics, Orphanet
• brain abnormalities, neurodegeneration, and dysosteosclerosis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-150068065-A-G is Benign according to our data. Variant chr5-150068065-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 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.1626+150T>C		intron	N/A	NP_001275634.1
	CSF1R	NM_001349736.2		c.1626+150T>C		intron	N/A	NP_001336665.1
	CSF1R	NM_001375320.1		c.1626+150T>C		intron	N/A	NP_001362249.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.1626+150T>C		intron	N/A	ENSP00000501699.1
	CSF1R	ENST00000286301.7	TSL:1	c.1626+150T>C		intron	N/A	ENSP00000286301.3
	CSF1R	ENST00000504875.5	TSL:1	n.1626+150T>C		intron	N/A	ENSP00000422212.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100680 AN: 151854 Hom.: 33660 Cov.: 31

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.643 AC: 300416 AN: 466992 Hom.: 97894 AF XY: 0.644 AC XY: 159558 AN XY: 247798

African (AFR) AF: 0.710 AC: 9191 AN: 12954

American (AMR) AF: 0.689 AC: 16291 AN: 23644

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 8103 AN: 13350

East Asian (EAS) AF: 0.537 AC: 16789 AN: 31286

South Asian (SAS) AF: 0.682 AC: 31709 AN: 46508

European-Finnish (FIN) AF: 0.732 AC: 22543 AN: 30792

Middle Eastern (MID) AF: 0.554 AC: 1504 AN: 2716

European-Non Finnish (NFE) AF: 0.635 AC: 177472 AN: 279486

Other (OTH) AF: 0.640 AC: 16814 AN: 26256

GnomAD4 genome AF: 0.663 AC: 100778 AN: 151972 Hom.: 33702 Cov.: 31 AF XY: 0.669 AC XY: 49668 AN XY: 74260

African (AFR) AF: 0.705 AC: 29246 AN: 41458

American (AMR) AF: 0.656 AC: 10029 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2107 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3077 AN: 5134

South Asian (SAS) AF: 0.683 AC: 3286 AN: 4812

European-Finnish (FIN) AF: 0.741 AC: 7830 AN: 10566

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43306 AN: 67950

Other (OTH) AF: 0.609 AC: 1281 AN: 2102

Alfa AF: 0.652 Hom.: 8251

Bravo AF: 0.657

Asia WGS AF: 0.657 AC: 2285 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		-0.64
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: rs216150; hg19: chr5-149447628; COSMIC: COSV53831655; COSMIC: COSV53831655;