NM_000757.6:c.876G>A

Variant names:

• chr1-109923497-G-A
• rs12721513
• NM_000757.6:c.876G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000757.6(CSF1):​c.876G>A​(p.Glu292Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00565 in 1,614,120 control chromosomes in the GnomAD database, including 385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (200 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (185 hom.)
• Consequence: CSF1 NM_000757.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.775
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-109923497-G-A is Benign according to our data. Variant chr1-109923497-G-A is described in ClinVar as Benign. ClinVar VariationId is 775573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.775 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000757.6. 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.876G>A	p.Glu292Glu	synonymous	Exon 6 of 9	NP_000748.4
	CSF1	NM_172212.3		c.876G>A	p.Glu292Glu	synonymous	Exon 6 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.876G>A	p.Glu292Glu	synonymous	Exon 6 of 9	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.876G>A	p.Glu292Glu	synonymous	Exon 6 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.876G>A	p.Glu292Glu	synonymous	Exon 6 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.876G>A	p.Glu292Glu	synonymous	Exon 6 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4186 AN: 152140 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00785 AC: 1971 AN: 251202 AF XY: 0.00577

Gnomad AFR exome AF: 0.0973

Gnomad AMR exome AF: 0.00680

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00337 AC: 4925 AN: 1461862 Hom.: 185 Cov.: 31 AF XY: 0.00298 AC XY: 2167 AN XY: 727238

African (AFR) AF: 0.0993 AC: 3324 AN: 33480

American (AMR) AF: 0.00754 AC: 337 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5768

European-Non Finnish (NFE) AF: 0.000647 AC: 719 AN: 1111996

Other (OTH) AF: 0.00767 AC: 463 AN: 60390

GnomAD4 genome AF: 0.0275 AC: 4192 AN: 152258 Hom.: 200 Cov.: 32 AF XY: 0.0266 AC XY: 1977 AN XY: 74442

African (AFR) AF: 0.0930 AC: 3861 AN: 41530

American (AMR) AF: 0.0137 AC: 210 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68008

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0128 Hom.: 41

Bravo AF: 0.0314

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.00174

EpiControl AF: 0.00166

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.79
PhyloP100		-0.78
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: rs12721513; hg19: chr1-110466119;