chr1-109911033-C-A

Variant names:

• chr1-109911033-C-A
• rs779110244
• NM_000757.6:c.10C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000757.6(CSF1):​c.10C>A​(p.Pro4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 990,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P4S) 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: -0.139
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081980735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.10C>A	p.Pro4Thr	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.10C>A	p.Pro4Thr	missense_variant	Exon 1 of 9	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 990158 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 470146

African (AFR) AF: 0.00 AC: 0 AN: 19422

American (AMR) AF: 0.00 AC: 0 AN: 7350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10432

East Asian (EAS) AF: 0.00 AC: 0 AN: 16030

South Asian (SAS) AF: 0.00 AC: 0 AN: 21346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2438

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 862614

Other (OTH) AF: 0.00 AC: 0 AN: 36458

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.098	.;T;T;T;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.74	T;.;T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.082	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	.;L;.;L;L;L
PhyloP100		-0.14
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.16	N;N;N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.11	T;T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T;T
Polyphen		0.24, 0.065, 0.64	.;B;.;B;B;P
Vest4		0.12, 0.12, 0.10, 0.12
MutPred		0.43		Gain of glycosylation at P4 (P = 0.0321);Gain of glycosylation at P4 (P = 0.0321);Gain of glycosylation at P4 (P = 0.0321);Gain of glycosylation at P4 (P = 0.0321);Gain of glycosylation at P4 (P = 0.0321);Gain of glycosylation at P4 (P = 0.0321);
MVP		0.22
MPC		0.18
ClinPred		0.084	T
GERP RS		2.0
PromoterAI		0.0026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.049
gMVP		0.18
Mutation Taster		=91/9	polymorphism

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: rs779110244; hg19: chr1-110453655;