rs13188584

Variant names:

• chr5-150080011-C-T
• rs13188584
• NM_001288705.3:c.592+41G>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.592+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,591,254 control chromosomes in the GnomAD database, including 12,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1130 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11460 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 12 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=-0.9).
• BP6: Variant 5-150080011-C-T is Benign according to our data. Variant chr5-150080011-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1R	NM_001288705.3	c.592+41G>A		intron_variant	Intron 3 of 20	ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1	c.592+41G>A		intron_variant	Intron 3 of 20		NM_001288705.3	ENSP00000501699.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18352 AN: 152140 Hom.: 1130 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.120 AC: 28481 AN: 237290 AF XY: 0.120

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.0748

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.124 AC: 178210 AN: 1438998 Hom.: 11460 Cov.: 33 AF XY: 0.124 AC XY: 88090 AN XY: 712218

African (AFR) AF: 0.127 AC: 4209 AN: 33230

American (AMR) AF: 0.117 AC: 5136 AN: 44010

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3520 AN: 24916

East Asian (EAS) AF: 0.120 AC: 4733 AN: 39348

South Asian (SAS) AF: 0.130 AC: 10781 AN: 83028

European-Finnish (FIN) AF: 0.0805 AC: 4099 AN: 50904

Middle Eastern (MID) AF: 0.132 AC: 715 AN: 5410

European-Non Finnish (NFE) AF: 0.125 AC: 136914 AN: 1098702

Other (OTH) AF: 0.136 AC: 8103 AN: 59450

GnomAD4 genome AF: 0.121 AC: 18356 AN: 152256 Hom.: 1130 Cov.: 33 AF XY: 0.120 AC XY: 8901 AN XY: 74450

African (AFR) AF: 0.119 AC: 4948 AN: 41554

American (AMR) AF: 0.130 AC: 1994 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.139 AC: 718 AN: 5166

South Asian (SAS) AF: 0.127 AC: 612 AN: 4822

European-Finnish (FIN) AF: 0.0706 AC: 750 AN: 10620

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8421 AN: 68008

Other (OTH) AF: 0.129 AC: 272 AN: 2106

Alfa AF: 0.124 Hom.: 992

Bravo AF: 0.125

Asia WGS AF: 0.152 AC: 526 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0070
DANN	Benign	0.75
PhyloP100		-1.3
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: rs13188584; hg19: chr5-149459574; COSMIC: COSV53831180; COSMIC: COSV53831180;