rs333948

Variant names:

• chr1-109927970-G-A
• rs333948
• NM_000757.6:c.*14-882G>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.*14-882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,172 control chromosomes in the GnomAD database, including 3,925 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 0.20 (3925 hom., cov: 32)
• Consequence: CSF1 NM_000757.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 5 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.*14-882G>A		intron_variant	Intron 8 of 8	ENST00000329608.11	NP_000748.4
CSF1	NM_172211.4	c.*14-882G>A		intron_variant	Intron 8 of 8		NP_757350.2
CSF1	XM_017000369.1	c.*14-882G>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.*14-882G>A		intron_variant	Intron 8 of 8	1	NM_000757.6	ENSP00000327513.6
CSF1	ENST00000420111.6	c.*14-882G>A		intron_variant	Intron 8 of 8	5		ENSP00000407317.2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31045 AN: 152054 Hom.: 3922 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.204 AC: 31057 AN: 152172 Hom.: 3925 Cov.: 32 AF XY: 0.210 AC XY: 15645 AN XY: 74366

African (AFR) AF: 0.0800 AC: 3323 AN: 41544

American (AMR) AF: 0.291 AC: 4442 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 800 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2095 AN: 5168

South Asian (SAS) AF: 0.455 AC: 2189 AN: 4814

European-Finnish (FIN) AF: 0.213 AC: 2249 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15118 AN: 68006

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.185 Hom.: 1620

Bravo AF: 0.203

Asia WGS AF: 0.408 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.0
DANN	Benign	0.74
PhyloP100		1.5
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: rs333948; hg19: chr1-110470592;