rs13188584

chr5-150080011-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	UniProt
CSF1R	NM_001288705.3	c.592+41G>A		intron_variant		ENST00000675795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1R	ENST00000675795.1	c.592+41G>A		intron_variant			NM_001288705.3	P1

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

GnomAD3 exomes AF: 0.120 AC: 28481 AN: 237290 Hom.: 1753 AF XY: 0.120 AC XY: 15367 AN XY: 127632

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 SAS exome AF: 0.131

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

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0805

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.136

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.129

Alfa AF: 0.124 Hom.: 814

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0070
Dann	Benign	0.75

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: rs13188584; hg19: chr5-149459574; COSMIC: COSV53831180; COSMIC: COSV53831180;