rs3093040

chr1-109927802-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000757.6(CSF1):c.*14-1050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,150 control chromosomes in the GnomAD database, including 7,465 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7465 hom., cov: 32)
• Consequence: CSF1 NM_000757.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1	NM_000757.6	c.*14-1050G>A		intron_variant		ENST00000329608.11
CSF1	NM_172211.4	c.*14-1050G>A		intron_variant
CSF1	XM_017000369.1	c.*14-1050G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11	c.*14-1050G>A		intron_variant		1	NM_000757.6	P4
CSF1	ENST00000420111.6	c.*14-1050G>A		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42908 AN: 152032 Hom.: 7465 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 42900 AN: 152150 Hom.: 7465 Cov.: 32 AF XY: 0.278 AC XY: 20679 AN XY: 74374

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.304

Alfa AF: 0.352 Hom.: 7512

Bravo AF: 0.263

Asia WGS AF: 0.102 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	11
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs3093040; hg19: chr1-110470424;