rs2229166

Variant names:

• chr1-109924188-C-A
• rs2229166
• NM_000757.6:c.1567C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109924188-C-A
• chr1-109924188-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000757.6(CSF1):​c.1567C>A​(p.Arg523Arg) 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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000757.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	NM_000757.6	MANE Select	c.1567C>A	p.Arg523Arg	splice_region synonymous	Exon 6 of 9	NP_000748.4
	CSF1	NM_172212.3		c.1567C>A	p.Arg523Arg	splice_region synonymous	Exon 6 of 9	NP_757351.2
	CSF1	NM_172210.3		c.1219C>A	p.Arg407Arg	splice_region synonymous	Exon 7 of 9	NP_757349.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	ENST00000329608.11	TSL:1 MANE Select	c.1567C>A	p.Arg523Arg	splice_region synonymous	Exon 6 of 9	ENSP00000327513.6
	CSF1	ENST00000369802.7	TSL:1	c.1567C>A	p.Arg523Arg	splice_region synonymous	Exon 6 of 9	ENSP00000358817.3
	CSF1	ENST00000369801.1	TSL:1	c.1219C>A	p.Arg407Arg	splice_region synonymous	Exon 7 of 9	ENSP00000358816.1

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

GnomAD2 exomes AF: 0.223 AC: 52478 AN: 235314 AF XY: 0.217

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 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

African (AFR) AF: 0.384 AC: 12745 AN: 33200

American (AMR) AF: 0.233 AC: 10117 AN: 43506

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3200 AN: 25104

East Asian (EAS) AF: 0.541 AC: 21447 AN: 39616

South Asian (SAS) AF: 0.229 AC: 19424 AN: 84650

European-Finnish (FIN) AF: 0.174 AC: 9120 AN: 52334

Middle Eastern (MID) AF: 0.133 AC: 754 AN: 5648

European-Non Finnish (NFE) AF: 0.169 AC: 187293 AN: 1105920

Other (OTH) AF: 0.198 AC: 11841 AN: 59790

GnomAD4 genome AF: 0.244 AC: 37088 AN: 151916 Hom.: 5441 Cov.: 31 AF XY: 0.247 AC XY: 18347 AN XY: 74230

African (AFR) AF: 0.382 AC: 15808 AN: 41394

American (AMR) AF: 0.226 AC: 3447 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2686 AN: 5140

South Asian (SAS) AF: 0.231 AC: 1110 AN: 4796

European-Finnish (FIN) AF: 0.171 AC: 1806 AN: 10552

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11132 AN: 67990

Other (OTH) AF: 0.212 AC: 446 AN: 2108

Alfa AF: 0.174 Hom.: 2128

Bravo AF: 0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

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