rs10077461

Variant names:

• chr5-150079368-C-A
• rs10077461
• NM_001288705.3:c.592+684G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150079368-C-A
• chr5-150079368-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005211.4(CSF1R):​c.592+684G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,212 control chromosomes in the GnomAD database, including 4,491 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 0.19 (4491 hom., cov: 33)
• Consequence: CSF1R NM_005211.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005211.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	NM_001288705.3	MANE Select	c.592+684G>T		intron	N/A	NP_001275634.1
	CSF1R	NM_001349736.2		c.592+684G>T		intron	N/A	NP_001336665.1
	CSF1R	NM_001375320.1		c.592+684G>T		intron	N/A	NP_001362249.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	ENST00000675795.1	MANE Select	c.592+684G>T		intron	N/A	ENSP00000501699.1
	CSF1R	ENST00000286301.7	TSL:1	c.592+684G>T		intron	N/A	ENSP00000286301.3
	CSF1R	ENST00000543093.1	TSL:1	c.592+684G>T		intron	N/A	ENSP00000445282.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29279 AN: 152094 Hom.: 4485 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.193 AC: 29312 AN: 152212 Hom.: 4491 Cov.: 33 AF XY: 0.195 AC XY: 14485 AN XY: 74438

African (AFR) AF: 0.369 AC: 15302 AN: 41508

American (AMR) AF: 0.252 AC: 3853 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2854 AN: 5170

South Asian (SAS) AF: 0.147 AC: 709 AN: 4830

European-Finnish (FIN) AF: 0.0502 AC: 533 AN: 10622

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.0740 AC: 5030 AN: 68010

Other (OTH) AF: 0.180 AC: 378 AN: 2104

Alfa AF: 0.117 Hom.: 690

Bravo AF: 0.220

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		-0.48
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: rs10077461; hg19: chr5-149458931;