rs333970

Variant names:

• chr1-109923716-C-A
• rs333970
• NM_000757.6:c.1095C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109923716-C-A
• chr1-109923716-C-G
• chr1-109923716-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172210.3(CSF1):​c.1090+5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,612,420 control chromosomes in the GnomAD database, including 279,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (20144 hom., cov: 33)
  • Exomes 𝑓: 0.59 (259512 hom.)
• Consequence: CSF1 NM_172210.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 30 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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172210.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	NM_000757.6	MANE Select	c.1095C>A	p.Thr365Thr	synonymous	Exon 6 of 9	NP_000748.4
	CSF1	NM_172212.3		c.1095C>A	p.Thr365Thr	synonymous	Exon 6 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.1090+5C>A		splice_region intron	N/A	NP_757349.2	P09603-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	ENST00000329608.11	TSL:1 MANE Select	c.1095C>A	p.Thr365Thr	synonymous	Exon 6 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.1095C>A	p.Thr365Thr	synonymous	Exon 6 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.1090+5C>A		splice_region intron	N/A	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73135 AN: 151960 Hom.: 20143 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.515

GnomAD2 exomes AF: 0.567 AC: 141740 AN: 250112 AF XY: 0.574

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.543

Gnomad EAS exome AF: 0.431

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.609

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.591 AC: 862869 AN: 1460344 Hom.: 259512 Cov.: 73 AF XY: 0.592 AC XY: 430328 AN XY: 726316

African (AFR) AF: 0.181 AC: 6065 AN: 33460

American (AMR) AF: 0.600 AC: 26752 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 14017 AN: 25988

East Asian (EAS) AF: 0.395 AC: 15691 AN: 39674

South Asian (SAS) AF: 0.603 AC: 51864 AN: 86040

European-Finnish (FIN) AF: 0.633 AC: 33773 AN: 53346

Middle Eastern (MID) AF: 0.608 AC: 3494 AN: 5746

European-Non Finnish (NFE) AF: 0.609 AC: 676957 AN: 1111202

Other (OTH) AF: 0.568 AC: 34256 AN: 60324

GnomAD4 genome AF: 0.481 AC: 73143 AN: 152076 Hom.: 20144 Cov.: 33 AF XY: 0.483 AC XY: 35898 AN XY: 74344

African (AFR) AF: 0.193 AC: 7995 AN: 41502

American (AMR) AF: 0.552 AC: 8448 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2120 AN: 5140

South Asian (SAS) AF: 0.587 AC: 2832 AN: 4826

European-Finnish (FIN) AF: 0.651 AC: 6900 AN: 10592

Middle Eastern (MID) AF: 0.559 AC: 162 AN: 290

European-Non Finnish (NFE) AF: 0.607 AC: 41251 AN: 67942

Other (OTH) AF: 0.518 AC: 1095 AN: 2112

Alfa AF: 0.572 Hom.: 53202

Bravo AF: 0.461

Asia WGS AF: 0.485 AC: 1690 AN: 3478

EpiCase AF: 0.612

EpiControl AF: 0.617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs333970; hg19: chr1-110466338; COSMIC: COSV60032931; COSMIC: COSV60032931;