rs10077461

chr5-150079368-C-Achr5-150079368-C-T

Variant summary

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

The NM_001288705.3(CSF1R):c.592+684G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,212 control chromosomes in the GnomAD database, including 4,491 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 0.19 (4491 hom., cov: 33)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1R	NM_001288705.3	c.592+684G>T		intron_variant		ENST00000675795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1R	ENST00000675795.1	c.592+684G>T		intron_variant			NM_001288705.3	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29279 AN: 152094 Hom.: 4485 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.193 AC: 29312 AN: 152212 Hom.: 4491 Cov.: 33 AF XY: 0.195 AC XY: 14485 AN XY: 74438

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.180

Alfa AF: 0.110 Hom.: 365

Bravo AF: 0.220

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.72

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: rs10077461; hg19: chr5-149458931;