rs3093040

Variant names:

• chr1-109927802-G-A
• rs3093040
• NM_000757.6:c.*14-1050G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.*14-1050G>A		intron_variant	Intron 8 of 8	ENST00000329608.11	NP_000748.4
CSF1	NM_172211.4	c.*14-1050G>A		intron_variant	Intron 8 of 8		NP_757350.2
CSF1	XM_017000369.1	c.*14-1050G>A		intron_variant	Intron 8 of 8		XP_016855858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.*14-1050G>A		intron_variant	Intron 8 of 8	1	NM_000757.6	ENSP00000327513.6
CSF1	ENST00000420111.6	c.*14-1050G>A		intron_variant	Intron 8 of 8	5		ENSP00000407317.2

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

African (AFR) AF: 0.113 AC: 4678 AN: 41530

American (AMR) AF: 0.272 AC: 4151 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5190

South Asian (SAS) AF: 0.185 AC: 894 AN: 4822

European-Finnish (FIN) AF: 0.435 AC: 4590 AN: 10554

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26465 AN: 67986

Other (OTH) AF: 0.304 AC: 641 AN: 2108

Alfa AF: 0.351 Hom.: 8804

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
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093040; hg19: chr1-110470424;