chr5-150054033-T-G

Variant names:

• chr5-150054033-T-G
• rs2066934
• NM_001288705.3:c.*36A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001288705.3(CSF1R):​c.*36A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,604,760 control chromosomes in the GnomAD database, including 477,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51083 hom., cov: 31)
  • Exomes 𝑓: 0.76 (426291 hom.)
• Consequence: CSF1R NM_001288705.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.659
• Publications: 21 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: Orphanet, Genomics England PanelApp, Ambry Genetics
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-150054033-T-G is Benign according to our data. Variant chr5-150054033-T-G is described in ClinVar as Benign. ClinVar VariationId is 352120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 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.*36A>C		3_prime_UTR	Exon 21 of 21	NP_001275634.1	P07333-1
	CSF1R	NM_001349736.2		c.*36A>C		3_prime_UTR	Exon 23 of 23	NP_001336665.1	P07333-1
	CSF1R	NM_001375320.1		c.*36A>C		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.*36A>C		3_prime_UTR	Exon 21 of 21	ENSP00000501699.1	P07333-1
	CSF1R	ENST00000286301.7	TSL:1	c.*36A>C		3_prime_UTR	Exon 22 of 22	ENSP00000286301.3	P07333-1
	CSF1R	ENST00000504875.5	TSL:1	n.*776A>C		non_coding_transcript_exon	Exon 20 of 20	ENSP00000422212.1	E9PEK4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123736 AN: 151584 Hom.: 51032 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.785

GnomAD2 exomes AF: 0.770 AC: 187786 AN: 243844 AF XY: 0.761

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.779

Gnomad ASJ exome AF: 0.800

Gnomad EAS exome AF: 0.735

Gnomad FIN exome AF: 0.802

Gnomad NFE exome AF: 0.762

Gnomad OTH exome AF: 0.769

GnomAD4 exome AF: 0.765 AC: 1111042 AN: 1453054 Hom.: 426291 Cov.: 30 AF XY: 0.761 AC XY: 550300 AN XY: 722792

African (AFR) AF: 0.953 AC: 31742 AN: 33320

American (AMR) AF: 0.778 AC: 34392 AN: 44186

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 20875 AN: 26032

East Asian (EAS) AF: 0.674 AC: 26603 AN: 39472

South Asian (SAS) AF: 0.684 AC: 58317 AN: 85298

European-Finnish (FIN) AF: 0.809 AC: 42896 AN: 53020

Middle Eastern (MID) AF: 0.758 AC: 4324 AN: 5706

European-Non Finnish (NFE) AF: 0.764 AC: 845258 AN: 1105944

Other (OTH) AF: 0.776 AC: 46635 AN: 60076

GnomAD4 genome AF: 0.816 AC: 123841 AN: 151706 Hom.: 51083 Cov.: 31 AF XY: 0.815 AC XY: 60410 AN XY: 74126

African (AFR) AF: 0.946 AC: 39189 AN: 41410

American (AMR) AF: 0.784 AC: 11977 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2794 AN: 3466

East Asian (EAS) AF: 0.716 AC: 3664 AN: 5114

South Asian (SAS) AF: 0.685 AC: 3292 AN: 4808

European-Finnish (FIN) AF: 0.806 AC: 8494 AN: 10534

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 51989 AN: 67792

Other (OTH) AF: 0.782 AC: 1650 AN: 2110

Alfa AF: 0.785 Hom.: 12382

Bravo AF: 0.821

Asia WGS AF: 0.730 AC: 2540 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary diffuse leukoencephalopathy with spheroids (2)
-	-	1	Brain abnormalities, neurodegeneration, and dysosteosclerosis (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.23
PhyloP100		0.66
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: rs2066934; hg19: chr5-149433596; COSMIC: COSV53831508; COSMIC: COSV53831508;