chr5-150061081-C-T

Variant names:

• chr5-150061081-C-T
• rs170037
• NM_001288705.3:c.1859-109G>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.1859-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 730,412 control chromosomes in the GnomAD database, including 113,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19793 hom., cov: 30)
  • Exomes 𝑓: 0.56 (93307 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.923
• Publications: 10 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=-0.82).
• BP6: Variant 5-150061081-C-T is Benign according to our data. Variant chr5-150061081-C-T is described in ClinVar as Benign. ClinVar VariationId is 1220882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1R	NM_001288705.3	c.1859-109G>A		intron_variant	Intron 12 of 20	ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1	c.1859-109G>A		intron_variant	Intron 12 of 20		NM_001288705.3	ENSP00000501699.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74315 AN: 151748 Hom.: 19796 Cov.: 30

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.559 AC: 323371 AN: 578544 Hom.: 93307 AF XY: 0.560 AC XY: 168560 AN XY: 301174

African (AFR) AF: 0.279 AC: 4428 AN: 15894

American (AMR) AF: 0.417 AC: 11893 AN: 28552

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 9221 AN: 16908

East Asian (EAS) AF: 0.424 AC: 13361 AN: 31520

South Asian (SAS) AF: 0.517 AC: 26416 AN: 51140

European-Finnish (FIN) AF: 0.673 AC: 22888 AN: 33988

Middle Eastern (MID) AF: 0.507 AC: 1967 AN: 3880

European-Non Finnish (NFE) AF: 0.592 AC: 216946 AN: 366218

Other (OTH) AF: 0.534 AC: 16251 AN: 30444

GnomAD4 genome AF: 0.489 AC: 74325 AN: 151868 Hom.: 19793 Cov.: 30 AF XY: 0.492 AC XY: 36513 AN XY: 74224

African (AFR) AF: 0.281 AC: 11640 AN: 41412

American (AMR) AF: 0.425 AC: 6493 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2328 AN: 5152

South Asian (SAS) AF: 0.517 AC: 2478 AN: 4794

European-Finnish (FIN) AF: 0.676 AC: 7142 AN: 10564

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40740 AN: 67892

Other (OTH) AF: 0.471 AC: 994 AN: 2110

Alfa AF: 0.529 Hom.: 8672

Bravo AF: 0.461

Asia WGS AF: 0.432 AC: 1500 AN: 3476

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	-0.82
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.92
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: rs170037; hg19: chr5-149440644; COSMIC: COSV53831573;