rs2066934

Positions:

chr5-150054033-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001288705.3(CSF1R):c.*36A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,604,760 control chromosomes in the GnomAD database, including 477,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51083 hom., cov: 31)

Exomes 𝑓: 0.76 ( 426291 hom. )

Consequence

CSF1R
NM_001288705.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.659

Variant links:

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]

CSF1R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-150054033-T-G is Benign according to our data. Variant chr5-150054033-T-G is described in ClinVar as [Benign]. Clinvar id is 352120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1R	NM_001288705.3 linkuse as main transcript	c.*36A>C		3_prime_UTR_variant	21/21	ENST00000675795.1	NP_001275634.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1R	ENST00000675795.1 linkuse as main transcript	c.*36A>C	3_prime_UTR_variant	21/21		NM_001288705.3	ENSP00000501699	P1	P07333-1
CSF1R	ENST00000286301.7 linkuse as main transcript	c.*36A>C	3_prime_UTR_variant	22/22	1		ENSP00000286301	P1	P07333-1
CSF1R	ENST00000504875.5 linkuse as main transcript	c.*776A>C	3_prime_UTR_variant, NMD_transcript_variant	20/20	1		ENSP00000422212
CSF1R	ENST00000509861.1 linkuse as main transcript	n.691A>C	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

123736

AN:

151584

Hom.:

51032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.946

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.784

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.806

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.785

GnomAD3 exomes

AF:

0.770

AC:

187786

AN:

243844

Hom.:

72716

AF XY:

0.761

AC XY:

100367

AN XY:

131870

show subpopulations

Gnomad AFR exome

AF:

0.950

Gnomad AMR exome

AF:

0.779

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.735

Gnomad SAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.802

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.769

GnomAD4 exome

AF:

0.765

AC:

1111042

AN:

1453054

Hom.:

426291

Cov.:

AF XY:

0.761

AC XY:

550300

AN XY:

722792

show subpopulations

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.778

Gnomad4 ASJ exome

AF:

0.802

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.684

Gnomad4 FIN exome

AF:

0.809

Gnomad4 NFE exome

AF:

0.764

Gnomad4 OTH exome

AF:

0.776

GnomAD4 genome

AF:

0.816

AC:

123841

AN:

151706

Hom.:

51083

Cov.:

AF XY:

0.815

AC XY:

60410

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.946

Gnomad4 AMR

AF:

0.784

Gnomad4 ASJ

AF:

0.806

Gnomad4 EAS

AF:

0.716

Gnomad4 SAS

AF:

0.685

Gnomad4 FIN

AF:

0.806

Gnomad4 NFE

AF:

0.767

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.785

Hom.:

12382

Bravo

AF:

0.821

Asia WGS

AF:

0.730

AC:

2540

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary diffuse leukoencephalopathy with spheroids

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Brain abnormalities, neurodegeneration, and dysosteosclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.3

DANN

Benign

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over