rs3093037

chr1-109929284-C-T

Variant summary

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

The NM_000757.6(CSF1):c.*446C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,798 control chromosomes in the GnomAD database, including 1,754 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 0.14 (1753 hom., cov: 33)
  • Exomes 𝑓: 0.068 (1 hom.)
• Consequence: CSF1 NM_000757.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1	NM_000757.6	c.*446C>T		3_prime_UTR_variant	9/9	ENST00000329608.11
CSF1	NM_172211.4	c.*446C>T		3_prime_UTR_variant	9/9
CSF1	XM_017000369.1	c.*446C>T		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11	c.*446C>T		3_prime_UTR_variant	9/9	1	NM_000757.6	P4

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21198 AN: 152152 Hom.: 1751 Cov.: 33

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.0682 AC: 36 AN: 528 Hom.: 1 Cov.: 0 AF XY: 0.0744 AC XY: 25 AN XY: 336

Gnomad4 FIN exome AF: 0.0563

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.139 AC: 21196 AN: 152270 Hom.: 1753 Cov.: 33 AF XY: 0.133 AC XY: 9893 AN XY: 74454

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0822

Gnomad4 FIN AF: 0.0881

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.153

Alfa AF: 0.181 Hom.: 2998

Bravo AF: 0.139

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.3
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3093037; hg19: chr1-110471906;