Variant 1-109923844-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000757.6(CSF1):c.1223T>C(p.Leu408Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,613,608 control chromosomes in the GnomAD database, including 116,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.39 ( 11701 hom., cov: 33)

Exomes 𝑓: 0.37 ( 104340 hom. )

Consequence

CSF1
NM_000757.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.34

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.0016703E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.1223T>C	p.Leu408Pro	missense_variant	6/9	ENST00000329608.11	NP_000748.4	P09603-1A0A024R0A1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.1223T>C	p.Leu408Pro	missense_variant	6/9	1	NM_000757.6	ENSP00000327513.6	P09603-1
CSF1	ENST00000369802.7 linkuse as main transcript	c.1223T>C	p.Leu408Pro	missense_variant	6/9	1		ENSP00000358817.3	P09603-1
CSF1	ENST00000369801.1 linkuse as main transcript	c.1090+133T>C		intron_variant		1		ENSP00000358816.1	P09603-2
CSF1	ENST00000420111.6 linkuse as main transcript	c.545-216T>C		intron_variant		5		ENSP00000407317.2	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58903

AN:

151914

Hom.:

11688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.376

AC:

94103

AN:

250576

Hom.:

18370

AF XY:

0.375

AC XY:

50877

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.428

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.443

Gnomad EAS exome

AF:

0.584

Gnomad SAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.374

AC:

546809

AN:

1461576

Hom.:

104340

Cov.:

AF XY:

0.374

AC XY:

271591

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.446

Gnomad4 EAS exome

AF:

0.604

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.380

GnomAD4 genome

AF:

0.388

AC:

58945

AN:

152032

Hom.:

11701

Cov.:

AF XY:

0.386

AC XY:

28656

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.433

Gnomad4 AMR

AF:

0.356

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.596

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.380

Hom.:

17845

Bravo

AF:

0.396

TwinsUK

AF:

0.392

AC:

1454

ALSPAC

AF:

0.381

AC:

1468

ESP6500AA

AF:

0.440

AC:

1940

ESP6500EA

AF:

0.373

AC:

3204

ExAC

AF:

0.380

AC:

46176

Asia WGS

AF:

0.460

AC:

1598

AN:

3478

EpiCase

AF:

0.368

EpiControl

AF:

0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.067

DANN

Benign

0.32

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.20

.;T

MetaRNN

Benign

0.0000040

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.63

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.050

N;N

REVEL

Benign

0.010

Sift

Benign

0.20

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0020

B;B

Vest4

0.027

MPC

0.18

ClinPred

0.025

GERP RS

-9.1

Varity_R

0.026

gMVP

0.21

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over