rs3733673

Variant names:

• chr5-150077930-A-G
• rs3733673
• NM_001288705.3:c.729+182T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-150077930-A-G
• chr5-150077930-A-C
• chr5-150077930-A-T

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.729+182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 147,126 control chromosomes in the GnomAD database, including 3,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (3380 hom., cov: 27)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.228
• Publications: 4 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, Orphanet, 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 5-150077930-A-G is Benign according to our data. Variant chr5-150077930-A-G is described in ClinVar as Benign. ClinVar VariationId is 1282210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 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.729+182T>C		intron	N/A	NP_001275634.1	P07333-1
	CSF1R	NM_001349736.2		c.729+182T>C		intron	N/A	NP_001336665.1	P07333-1
	CSF1R	NM_001375320.1		c.729+182T>C		intron	N/A	NP_001362249.1	P07333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.729+182T>C		intron	N/A	ENSP00000501699.1	P07333-1
	CSF1R	ENST00000286301.7	TSL:1	c.729+182T>C		intron	N/A	ENSP00000286301.3	P07333-1
	CSF1R	ENST00000543093.1	TSL:1	c.729+182T>C		intron	N/A	ENSP00000445282.1	P07333-2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22396 AN: 147026 Hom.: 3369 Cov.: 27

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0515

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.0542

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.0974

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.153 AC: 22456 AN: 147126 Hom.: 3380 Cov.: 27 AF XY: 0.153 AC XY: 10936 AN XY: 71400

African (AFR) AF: 0.378 AC: 15031 AN: 39732

American (AMR) AF: 0.205 AC: 3009 AN: 14676

Ashkenazi Jewish (ASJ) AF: 0.0515 AC: 177 AN: 3436

East Asian (EAS) AF: 0.236 AC: 1139 AN: 4834

South Asian (SAS) AF: 0.0546 AC: 249 AN: 4560

European-Finnish (FIN) AF: 0.0506 AC: 490 AN: 9688

Middle Eastern (MID) AF: 0.102 AC: 29 AN: 284

European-Non Finnish (NFE) AF: 0.0301 AC: 2019 AN: 66974

Other (OTH) AF: 0.152 AC: 311 AN: 2040

Alfa AF: 0.128 Hom.: 524

Bravo AF: 0.175

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

ClinVar submissions

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	-0.98
CADD	Benign	2.9
DANN	Benign	0.41
PhyloP100		-0.23
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3733673;

hg19: chr5-149457493;

COSMIC: COSV53846144;

COSMIC: COSV53846144;