NM_000757.6:c.535T>G

Variant names:

• chr1-109921985-T-G
• rs778137740
• NM_000757.6:c.535T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000757.6(CSF1):​c.535T>G​(p.Ser179Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,447,538 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.679
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20441046).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	NM_000757.6	MANE Select	c.535T>G	p.Ser179Ala	missense	Exon 5 of 9	NP_000748.4
	CSF1	NM_172212.3		c.535T>G	p.Ser179Ala	missense	Exon 5 of 9	NP_757351.2	P09603-1
	CSF1	NM_172210.3		c.535T>G	p.Ser179Ala	missense	Exon 5 of 9	NP_757349.2	P09603-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF1	ENST00000329608.11	TSL:1 MANE Select	c.535T>G	p.Ser179Ala	missense	Exon 5 of 9	ENSP00000327513.6	P09603-1
	CSF1	ENST00000369802.7	TSL:1	c.535T>G	p.Ser179Ala	missense	Exon 5 of 9	ENSP00000358817.3	P09603-1
	CSF1	ENST00000369801.1	TSL:1	c.535T>G	p.Ser179Ala	missense	Exon 5 of 9	ENSP00000358816.1	P09603-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 241996 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000225

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000829 AC: 12 AN: 1447538 Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8 AN XY: 718554

African (AFR) AF: 0.00 AC: 0 AN: 33120

American (AMR) AF: 0.00 AC: 0 AN: 43636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25746

East Asian (EAS) AF: 0.000307 AC: 12 AN: 39120

South Asian (SAS) AF: 0.00 AC: 0 AN: 84114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103104

Other (OTH) AF: 0.00 AC: 0 AN: 59798

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.68
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.092
Sift	Benign	0.051	T
Sift4G	Benign	0.42	T
Polyphen		0.51	P
Vest4		0.40
MutPred		0.71		Loss of disorder (P = 0.0526)
MVP		0.48
MPC		0.38
ClinPred		0.12	T
GERP RS		1.4
Varity_R		0.064
gMVP		0.21
Mutation Taster		=96/4	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: rs778137740; hg19: chr1-110464607;