1-109915651-G-T

Variant names:

• chr1-109915651-G-T
• NM_000757.6:c.180G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000757.6(CSF1):​c.180G>T​(p.Glu60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.180G>T	p.Glu60Asp	missense_variant	Exon 3 of 9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.180G>T	p.Glu60Asp	missense_variant	Exon 3 of 9	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.180G>T (p.E60D) alteration is located in exon 1 (coding exon 1) of the CSF1 gene. This alteration results from a G to T substitution at nucleotide position 180, causing the glutamic acid (E) at amino acid position 60 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T;T;.;T;T;T;.;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.86	D;D;D;.;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;.;.;M;.;M;M;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N;N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.013	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		0.99, 0.98, 0.99	.;.;.;D;.;D;D;D
Vest4		0.40, 0.40, 0.38, 0.39
MutPred		0.80		.;.;Loss of disorder (P = 0.2325);Loss of disorder (P = 0.2325);.;Loss of disorder (P = 0.2325);Loss of disorder (P = 0.2325);Loss of disorder (P = 0.2325);
MVP		0.56
MPC		0.49
ClinPred		0.84	D
GERP RS		3.5
Varity_R		0.50
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-110458273;