5-150053834-GA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001288705.3(CSF1R):c.*234del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 537,122 control chromosomes in the GnomAD database, including 174 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.036 (171 hom., cov: 28)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: CSF1R NM_001288705.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.01

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1R	NM_001288705.3	c.*234del		3_prime_UTR_variant	21/21	ENST00000675795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1R	ENST00000675795.1	c.*234del		3_prime_UTR_variant	21/21		NM_001288705.3	P1
CSF1R	ENST00000286301.7	c.*234del		3_prime_UTR_variant	22/22	1		P1
CSF1R	ENST00000504875.5	c.*974del		3_prime_UTR_variant, NMD_transcript_variant	20/20	1
CSF1R	ENST00000509861.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 3753 AN: 105144 Hom.: 170 Cov.: 28

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00856

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000634

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000381

Gnomad OTH AF: 0.0260

GnomAD4 exome AF: 0.00195 AC: 840 AN: 431866 Hom.: 3 Cov.: 3 AF XY: 0.00158 AC XY: 359 AN XY: 227372

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.0000355

Gnomad4 NFE exome AF: 0.000100

Gnomad4 OTH exome AF: 0.00392

GnomAD4 genome AF: 0.0358 AC: 3768 AN: 105256 Hom.: 171 Cov.: 28 AF XY: 0.0354 AC XY: 1810 AN XY: 51102

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.00854

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000635

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000381

Gnomad4 OTH AF: 0.0257

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary diffuse leukoencephalopathy with spheroids Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs376905470; hg19: chr5-149433397;