rs2229166

chr1-109924188-C-Achr1-109924188-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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

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]

ACMG classification

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	UniProt
CSF1	NM_000757.6	c.1567C>A	p.Arg523=	splice_region_variant, synonymous_variant	6/9	ENST00000329608.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11	c.1567C>A	p.Arg523=	splice_region_variant, synonymous_variant	6/9	1	NM_000757.6	P4
CSF1	ENST00000369802.7	c.1567C>A	p.Arg523=	splice_region_variant, synonymous_variant	6/9	1		P4
CSF1	ENST00000369801.1	c.1219C>A	p.Arg407=	splice_region_variant, synonymous_variant	7/9	1
CSF1	ENST00000420111.6	c.673C>A	p.Arg225=	splice_region_variant, synonymous_variant	6/9	5		A1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37045 AN: 151798 Hom.: 5434 Cov.: 31

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

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.: 36 AF XY: 0.190 AC XY: 136971 AN XY: 720460

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.: 31 AF XY: 0.247 AC XY: 18347 AN XY: 74230

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	13
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

Other links and lift over

dbSNP: rs2229166; hg19: chr1-110466810; COSMIC: COSV60032454; COSMIC: COSV60032454;