Variant rs2229166 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000757.6(CSF1):c.1567C>A(p.Arg523=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,601,684 control chromosomes in the GnomAD database, including 35,723 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5441 hom., cov: 31)

Exomes 𝑓: 0.19 ( 30282 hom. )

Consequence

CSF1
NM_000757.6 splice_region, synonymous

Scores

Splicing: ADA: 0.003060

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.991

Variant links:

Genes affected

CSF1 (HGNC:2432): (colony stimulating factor 1) The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. The encoded protein may be involved in development of the placenta. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

CSF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.991 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.1567C>A	p.Arg523=	splice_region_variant, synonymous_variant	6/9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.1567C>A	p.Arg523=	splice_region_variant, synonymous_variant	6/9	1	NM_000757.6	ENSP00000327513	P4	P09603-1
CSF1	ENST00000369802.7 linkuse as main transcript	c.1567C>A	p.Arg523=	splice_region_variant, synonymous_variant	6/9	1		ENSP00000358817	P4	P09603-1
CSF1	ENST00000369801.1 linkuse as main transcript	c.1219C>A	p.Arg407=	splice_region_variant, synonymous_variant	7/9	1		ENSP00000358816		P09603-2
CSF1	ENST00000420111.6 linkuse as main transcript	c.673C>A	p.Arg225=	splice_region_variant, synonymous_variant	6/9	5		ENSP00000407317	A1	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37045

AN:

151798

Hom.:

5434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.223

AC:

52478

AN:

235314

Hom.:

7117

AF XY:

0.217

AC XY:

27737

AN XY:

127876

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.190

AC:

275941

AN:

1449768

Hom.:

30282

Cov.:

AF XY:

0.190

AC XY:

136971

AN XY:

720460

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.244

AC:

37088

AN:

151916

Hom.:

5441

Cov.:

AF XY:

0.247

AC XY:

18347

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.523

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.155

Hom.:

1124

Bravo

AF:

0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0031

dbscSNV1_RF

Benign

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over