chr1-109912811-A-G

Position:

• chr1-109912811-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6	c.40-1448A>G		intron_variant		ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.40-1448A>G		intron_variant		1	NM_000757.6	ENSP00000327513	P4

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

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.00543

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.389

Alfa AF: 0.437 Hom.: 19155

Bravo AF: 0.370

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs915357; hg19: chr1-110455433;