rs216148

Positions:

• chr5-150066924-G-A

Variant summary

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

The NM_001288705.3(CSF1R):​c.1626+1291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,646 control chromosomes in the GnomAD database, including 6,050 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 0.23 (6043 hom., cov: 32)
  • Exomes 𝑓: 0.088 (7 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1R	NM_001288705.3	c.1626+1291C>T		intron_variant		ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1	c.1626+1291C>T		intron_variant			NM_001288705.3	ENSP00000501699	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34443 AN: 151798 Hom.: 6020 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.0877 AC: 64 AN: 730 Hom.: 7 AF XY: 0.0875 AC XY: 42 AN XY: 480

Gnomad4 AFR exome AF: 0.667

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.0619

Gnomad4 NFE exome AF: 0.0746

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.227 AC: 34518 AN: 151916 Hom.: 6043 Cov.: 32 AF XY: 0.228 AC XY: 16916 AN XY: 74268

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.0575

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.214

Alfa AF: 0.125 Hom.: 2455

Bravo AF: 0.252

Asia WGS AF: 0.356 AC: 1236 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.57

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: rs216148; hg19: chr5-149446487;