rs3829987

Positions:

• chr5-150077248-G-A
• chr5-150077248-G-C
• chr5-150077248-G-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.889+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,674 control chromosomes in the GnomAD database, including 8,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (3060 hom., cov: 32)
  • Exomes 𝑓: 0.051 (5424 hom.)
• Consequence: CSF1R NM_001288705.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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=-0.95).
• BP6: Variant 5-150077248-G-A is Benign according to our data. Variant chr5-150077248-G-A is described in ClinVar as [Benign]. Clinvar id is 1239548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1R	NM_001288705.3	c.889+28C>T		intron_variant		ENST00000675795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1R	ENST00000675795.1	c.889+28C>T		intron_variant			NM_001288705.3	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21764 AN: 152010 Hom.: 3047 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.101 AC: 25309 AN: 251444 Hom.: 2763 AF XY: 0.0861 AC XY: 11696 AN XY: 135914

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.226

Gnomad SAS exome AF: 0.0447

Gnomad FIN exome AF: 0.0502

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0757

GnomAD4 exome AF: 0.0513 AC: 75025 AN: 1461546 Hom.: 5424 Cov.: 32 AF XY: 0.0494 AC XY: 35942 AN XY: 727096

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.0497

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.0449

Gnomad4 FIN exome AF: 0.0492

Gnomad4 NFE exome AF: 0.0280

Gnomad4 OTH exome AF: 0.0758

GnomAD4 genome AF: 0.143 AC: 21824 AN: 152128 Hom.: 3060 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74368

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0478

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0612 Hom.: 787

Bravo AF: 0.166

Asia WGS AF: 0.172 AC: 600 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	-0.95
CADD	Benign	0.070
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3829987; hg19: chr5-149456811; COSMIC: COSV53829563; COSMIC: COSV53829563;