NM_000757.6:c.7G>C

Variant names:

• chr1-109911030-G-C
• NM_000757.6:c.7G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000757.6(CSF1):​c.7G>C​(p.Ala3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000998 in 1,001,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3949169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.7G>C	p.Ala3Pro	missense_variant	Exon 1 of 9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.7G>C	p.Ala3Pro	missense_variant	Exon 1 of 9	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.98e-7 AC: 1 AN: 1001760 Hom.: 0 Cov.: 30 AF XY: 0.00000210 AC XY: 1 AN XY: 476190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000919

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;T;T;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.65	T;.;T;T;T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;.;L;L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0, 0.18	.;D;.;D;B;D
Vest4		0.30, 0.29, 0.23, 0.22
MutPred		0.69		Gain of glycosylation at A3 (P = 0.0331);Gain of glycosylation at A3 (P = 0.0331);Gain of glycosylation at A3 (P = 0.0331);Gain of glycosylation at A3 (P = 0.0331);Gain of glycosylation at A3 (P = 0.0331);Gain of glycosylation at A3 (P = 0.0331);
MVP		0.29
MPC		0.61
ClinPred		0.88	D
GERP RS		2.0
Varity_R		0.33
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-110453652;