Variant chr1-109911033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000757.6(CSF1):c.10C>T(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,139,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CSF1
NM_000757.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.139

Variant links:

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]

CSF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028324246).

BS2

High AC in GnomAdExome4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.10C>T	p.Pro4Ser	missense_variant	1/9	ENST00000329608.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.10C>T	p.Pro4Ser	missense_variant	1/9	1	NM_000757.6	P4	P09603-1

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149354

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

10950

Hom.:

AF XY:

0.000160

AC XY:

AN XY:

6260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000364

AC:

AN:

990158

Hom.:

Cov.:

AF XY:

0.0000383

AC XY:

AN XY:

470146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000515

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000104

Gnomad4 OTH exome

AF:

0.0000549

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149354

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72790

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.000484

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.10C>T (p.P4S) alteration is located in exon 1 (coding exon 1) of the CSF1 gene. This alteration results from a C to T substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by a serine (S). 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

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.090

.;T;T;T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.64

T;.;T;T;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.028

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.20

.;N;.;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.15

N;N;N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.13

T;T;T;T;T;T

Sift4G

Benign

0.82

T;T;T;T;T;T

Polyphen

0.0090, 0.0030, 0.046

.;B;.;B;B;B

Vest4

0.10, 0.092, 0.086, 0.097

MutPred

0.44

Gain of glycosylation at P4 (P = 0.018);Gain of glycosylation at P4 (P = 0.018);Gain of glycosylation at P4 (P = 0.018);Gain of glycosylation at P4 (P = 0.018);Gain of glycosylation at P4 (P = 0.018);Gain of glycosylation at P4 (P = 0.018);

MVP

0.20

MPC

0.11

ClinPred

0.028

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.033

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over