chr5-150077248-G-A

Variant names:

• chr5-150077248-G-A
• rs3829987
• NM_001288705.3:c.889+28C>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.889+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,674 control chromosomes in the GnomAD database, including 8,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (3060 hom., cov: 32)
  • Exomes 𝑓: 0.051 (5424 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 13 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-150077248-G-A is Benign according to our data. Variant chr5-150077248-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1R	NM_001288705.3	MANE Select	c.889+28C>T		intron	N/A	NP_001275634.1
	CSF1R	NM_001349736.2		c.889+28C>T		intron	N/A	NP_001336665.1
	CSF1R	NM_001375320.1		c.889+28C>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.889+28C>T		intron	N/A	ENSP00000501699.1
	CSF1R	ENST00000286301.7	TSL:1	c.889+28C>T		intron	N/A	ENSP00000286301.3
	CSF1R	ENST00000543093.1	TSL:1	c.889+28C>T		intron	N/A	ENSP00000445282.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21764 AN: 152010 Hom.: 3047 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.101 AC: 25309 AN: 251444 AF XY: 0.0861

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.0502

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0757

GnomAD4 exome AF: 0.0513 AC: 75025 AN: 1461546 Hom.: 5424 Cov.: 32 AF XY: 0.0494 AC XY: 35942 AN XY: 727096

African (AFR) AF: 0.357 AC: 11933 AN: 33446

American (AMR) AF: 0.240 AC: 10749 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0497 AC: 1298 AN: 26124

East Asian (EAS) AF: 0.208 AC: 8243 AN: 39684

South Asian (SAS) AF: 0.0449 AC: 3874 AN: 86228

European-Finnish (FIN) AF: 0.0492 AC: 2627 AN: 53406

Middle Eastern (MID) AF: 0.108 AC: 623 AN: 5766

European-Non Finnish (NFE) AF: 0.0280 AC: 31101 AN: 1111794

Other (OTH) AF: 0.0758 AC: 4577 AN: 60382

GnomAD4 genome AF: 0.143 AC: 21824 AN: 152128 Hom.: 3060 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74368

African (AFR) AF: 0.345 AC: 14322 AN: 41482

American (AMR) AF: 0.198 AC: 3020 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1169 AN: 5158

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4822

European-Finnish (FIN) AF: 0.0478 AC: 507 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0299 AC: 2030 AN: 68004

Other (OTH) AF: 0.147 AC: 311 AN: 2116

Alfa AF: 0.0902 Hom.: 2254

Bravo AF: 0.166

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.070
DANN	Benign	0.45
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3829987; hg19: chr5-149456811; COSMIC: COSV53829563; COSMIC: COSV53829563;