5-150053759-G-T

Variant names:

• chr5-150053759-G-T
• rs41497048
• NM_001288705.3:c.*310C>A

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.*310C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 468,864 control chromosomes in the GnomAD database, including 2,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1484 hom., cov: 31)
  • Exomes 𝑓: 0.042 (849 hom.)
• Consequence: CSF1R NM_001288705.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230
• 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: 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=-0.82).
• BP6: Variant 5-150053759-G-T is Benign according to our data. Variant chr5-150053759-G-T is described in ClinVar as Benign. ClinVar VariationId is 352110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 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.*310C>A		3_prime_UTR	Exon 21 of 21	NP_001275634.1	P07333-1
	CSF1R	NM_001349736.2		c.*310C>A		3_prime_UTR	Exon 23 of 23	NP_001336665.1	P07333-1
	CSF1R	NM_001375320.1		c.*310C>A		3_prime_UTR	Exon 23 of 23	NP_001362249.1	P07333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.*310C>A		3_prime_UTR	Exon 21 of 21	ENSP00000501699.1	P07333-1
	CSF1R	ENST00000286301.7	TSL:1	c.*310C>A		3_prime_UTR	Exon 22 of 22	ENSP00000286301.3	P07333-1
	CSF1R	ENST00000504875.5	TSL:1	n.*1050C>A		non_coding_transcript_exon	Exon 20 of 20	ENSP00000422212.1	E9PEK4

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15164 AN: 151732 Hom.: 1483 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0970

GnomAD4 exome AF: 0.0422 AC: 13381 AN: 317016 Hom.: 849 Cov.: 0 AF XY: 0.0397 AC XY: 6538 AN XY: 164856

African (AFR) AF: 0.220 AC: 2210 AN: 10034

American (AMR) AF: 0.231 AC: 2738 AN: 11834

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 656 AN: 10694

East Asian (EAS) AF: 0.101 AC: 2075 AN: 20570

South Asian (SAS) AF: 0.0157 AC: 616 AN: 39218

European-Finnish (FIN) AF: 0.0301 AC: 456 AN: 15134

Middle Eastern (MID) AF: 0.0705 AC: 100 AN: 1418

European-Non Finnish (NFE) AF: 0.0186 AC: 3518 AN: 189268

Other (OTH) AF: 0.0537 AC: 1012 AN: 18846

GnomAD4 genome AF: 0.100 AC: 15186 AN: 151848 Hom.: 1484 Cov.: 31 AF XY: 0.101 AC XY: 7500 AN XY: 74234

African (AFR) AF: 0.226 AC: 9333 AN: 41244

American (AMR) AF: 0.207 AC: 3166 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.105 AC: 539 AN: 5130

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4810

European-Finnish (FIN) AF: 0.0308 AC: 327 AN: 10600

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0191 AC: 1302 AN: 68006

Other (OTH) AF: 0.0955 AC: 201 AN: 2104

Alfa AF: 0.0261 Hom.: 45

Bravo AF: 0.123

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary diffuse leukoencephalopathy with spheroids (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		0.023
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: rs41497048; hg19: chr5-149433322;