rs3093037

Variant names:

• chr1-109929284-C-T
• rs3093037
• NM_000757.6:c.*446C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.82).
• 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 rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.*446C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000329608.11	NP_000748.4
CSF1	NM_172211.4	c.*446C>T		3_prime_UTR_variant	Exon 9 of 9		NP_757350.2
CSF1	XM_017000369.1	c.*446C>T		3_prime_UTR_variant	Exon 9 of 9		XP_016855858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.*446C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000757.6	ENSP00000327513.6
CSF1	ENST00000420111.6	c.*446C>T		downstream_gene_variant		5		ENSP00000407317.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0563 AC: 24 AN: 426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.114 AC: 10 AN: 88

Other (OTH) AF: 0.167 AC: 2 AN: 12

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

African (AFR) AF: 0.0809 AC: 3359 AN: 41542

American (AMR) AF: 0.126 AC: 1924 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0822 AC: 397 AN: 4828

European-Finnish (FIN) AF: 0.0881 AC: 936 AN: 10624

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13056 AN: 68004

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.176 Hom.: 4107

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
PhyloP100		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3093037; hg19: chr1-110471906;