NM_000757.6:c.40-1448A>G

Variant names:

• chr1-109912811-A-G
• rs915357
• NM_000757.6:c.40-1448A>G

Variant summary

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

The NM_000757.6(CSF1):​c.40-1448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,984 control chromosomes in the GnomAD database, including 11,959 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 0.38 (11959 hom., cov: 32)
• Consequence: CSF1 NM_000757.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	NM_000757.6	MANE Select	c.40-1448A>G		intron	N/A	NP_000748.4
	CSF1	NM_172212.3		c.40-1448A>G		intron	N/A	NP_757351.2
	CSF1	NM_172210.3		c.40-1448A>G		intron	N/A	NP_757349.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	ENST00000329608.11	TSL:1 MANE Select	c.40-1448A>G		intron	N/A	ENSP00000327513.6
	CSF1	ENST00000369802.7	TSL:1	c.40-1448A>G		intron	N/A	ENSP00000358817.3
	CSF1	ENST00000369801.1	TSL:1	c.40-1448A>G		intron	N/A	ENSP00000358816.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58087 AN: 151866 Hom.: 11951 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.00541

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.382 AC: 58118 AN: 151984 Hom.: 11959 Cov.: 32 AF XY: 0.376 AC XY: 27937 AN XY: 74294

African (AFR) AF: 0.319 AC: 13199 AN: 41440

American (AMR) AF: 0.341 AC: 5208 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3472

East Asian (EAS) AF: 0.00543 AC: 28 AN: 5160

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4824

European-Finnish (FIN) AF: 0.467 AC: 4934 AN: 10562

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30873 AN: 67950

Other (OTH) AF: 0.389 AC: 816 AN: 2100

Alfa AF: 0.435 Hom.: 22888

Bravo AF: 0.370

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.39
PhyloP100		-2.3
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: rs915357; hg19: chr1-110455433;