rs6865659

Positions:

• chr5-150106209-A-G
• chr5-150106209-A-T

Variant summary

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

The ENST00000286301.7(CSF1R):​c.-181+7052T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,158 control chromosomes in the GnomAD database, including 6,747 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 0.29 (6747 hom., cov: 32)
• Consequence: CSF1R ENST00000286301.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1R	NM_001375320.1	c.-286+7052T>C		intron_variant			NP_001362249.1
CSF1R	NM_001375321.1	c.-396+7052T>C		intron_variant			NP_001362250.1
CSF1R	NM_005211.4	c.-181+7052T>C		intron_variant			NP_005202.2
CSF1R	NR_164679.1	n.105+7052T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000286301.7	c.-181+7052T>C		intron_variant		1		ENSP00000286301	P1
CSF1R	ENST00000511344.1	c.-396+7052T>C		intron_variant		4		ENSP00000421174

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44861 AN: 152040 Hom.: 6748 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.295 AC: 44876 AN: 152158 Hom.: 6747 Cov.: 32 AF XY: 0.290 AC XY: 21588 AN XY: 74392

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.322

Alfa AF: 0.312 Hom.: 4426

Bravo AF: 0.298

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.62

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: rs6865659; hg19: chr5-149485772;