5-150078565-T-C

Position:

• chr5-150078565-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288705.3(CSF1R):​c.593-317A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,198 control chromosomes in the GnomAD database, including 50,624 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 0.81 (50624 hom., cov: 33)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1R	NM_001288705.3	c.593-317A>G		intron_variant		ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1	c.593-317A>G		intron_variant			NM_001288705.3	ENSP00000501699.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123570 AN: 152080 Hom.: 50583 Cov.: 33

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.813 AC: 123664 AN: 152198 Hom.: 50624 Cov.: 33 AF XY: 0.816 AC XY: 60750 AN XY: 74408

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.781

Alfa AF: 0.801 Hom.: 6114

Bravo AF: 0.813

Asia WGS AF: 0.795 AC: 2768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.6
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2569076; hg19: chr5-149458128; COSMIC: COSV53831747; COSMIC: COSV53831747;