5-150053837-G-GC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001288705.3(CSF1R):c.*231_*232insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21046 hom., cov: 0)
  • Exomes 𝑓: 0.58 (74156 hom.)
• Consequence: CSF1R NM_001288705.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.788

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 -10 ACMG points.

• BP6: Variant 5-150053837-G-GC is Benign according to our data. Variant chr5-150053837-G-GC is described in ClinVar as [Benign]. Clinvar id is 352114.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1R	NM_001288705.3	c.*231_*232insG		3_prime_UTR_variant	21/21	ENST00000675795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1R	ENST00000675795.1	c.*231_*232insG		3_prime_UTR_variant	21/21		NM_001288705.3	P1
CSF1R	ENST00000286301.7	c.*231_*232insG		3_prime_UTR_variant	22/22	1		P1
CSF1R	ENST00000504875.5	c.*971_*972insG		3_prime_UTR_variant, NMD_transcript_variant	20/20	1
CSF1R	ENST00000509861.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 76909 AN: 149072 Hom.: 21046 Cov.: 0

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.578 AC: 250375 AN: 433266 Hom.: 74156 Cov.: 4 AF XY: 0.579 AC XY: 131987 AN XY: 227850

Gnomad4 AFR exome AF: 0.301

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.516 AC: 76933 AN: 149186 Hom.: 21046 Cov.: 0 AF XY: 0.517 AC XY: 37730 AN XY: 72940

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.490

Alfa AF: 0.421 Hom.: 1112

Bravo AF: 0.473

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary diffuse leukoencephalopathy with spheroids Benign:1

Benign, 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: rs3216780; hg19: chr5-149433400; COSMIC: COSV53830591; COSMIC: COSV53830591;