Variant rs2229165 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.1312G>A(p.Gly438Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,614,168 control chromosomes in the GnomAD database, including 2,236 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 0.059 ( 541 hom., cov: 34)

Exomes 𝑓: 0.023 ( 1695 hom. )

Consequence

CSF1
NM_000757.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

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=0.0017989278).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.1312G>A	p.Gly438Arg	missense_variant	6/9	ENST00000329608.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.1312G>A	p.Gly438Arg	missense_variant	6/9	1	NM_000757.6	P4	P09603-1
CSF1	ENST00000369802.7 linkuse as main transcript	c.1312G>A	p.Gly438Arg	missense_variant	6/9	1		P4	P09603-1
CSF1	ENST00000369801.1 linkuse as main transcript	c.1091-127G>A		intron_variant		1			P09603-2
CSF1	ENST00000420111.6 linkuse as main transcript	c.545-127G>A		intron_variant		5		A1	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8995

AN:

152224

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0754

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.0984

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.0535

GnomAD3 exomes

AF:

0.0496

AC:

12449

AN:

251096

Hom.:

733

AF XY:

0.0469

AC XY:

6365

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0919

Gnomad ASJ exome

AF:

0.00726

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.0932

Gnomad FIN exome

AF:

0.00758

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0231

AC:

33825

AN:

1461826

Hom.:

1695

Cov.:

AF XY:

0.0244

AC XY:

17744

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.0901

Gnomad4 ASJ exome

AF:

0.00719

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.0920

Gnomad4 FIN exome

AF:

0.00818

Gnomad4 NFE exome

AF:

0.00678

Gnomad4 OTH exome

AF:

0.0326

GnomAD4 genome

AF:

0.0592

AC:

9021

AN:

152342

Hom.:

541

Cov.:

AF XY:

0.0607

AC XY:

4518

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0756

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.0985

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.00723

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0200

Hom.:

297

Bravo

AF:

0.0685

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.141

AC:

622

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.0502

AC:

6097

Asia WGS

AF:

0.124

AC:

429

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

DANN

Benign

0.55

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.68

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.044

Sift

Benign

0.43

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.046

B;B

Vest4

0.058

MutPred

0.37

Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);

MPC

0.14

ClinPred

0.00083

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.12

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