Variant 1-109924188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000757.6(CSF1):c.1567C>T(p.Arg523Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,602,274 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 2 hom. )

Consequence

CSF1
NM_000757.6 missense, splice_region

Scores

Splicing: ADA: 0.4717

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.991

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12605402).

BS2

High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.1567C>T	p.Arg523Trp	missense_variant, splice_region_variant	6/9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.1567C>T	p.Arg523Trp	missense_variant, splice_region_variant	6/9	1	NM_000757.6	ENSP00000327513	P4	P09603-1
CSF1	ENST00000369802.7 linkuse as main transcript	c.1567C>T	p.Arg523Trp	missense_variant, splice_region_variant	6/9	1		ENSP00000358817	P4	P09603-1
CSF1	ENST00000369801.1 linkuse as main transcript	c.1219C>T	p.Arg407Trp	missense_variant, splice_region_variant	7/9	1		ENSP00000358816		P09603-2
CSF1	ENST00000420111.6 linkuse as main transcript	c.673C>T	p.Arg225Trp	missense_variant, splice_region_variant	6/9	5		ENSP00000407317	A1	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000234

AC:

AN:

235314

Hom.:

AF XY:

0.000242

AC XY:

AN XY:

127876

show subpopulations

Gnomad AFR exome

AF:

0.0000666

Gnomad AMR exome

AF:

0.0000905

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000398

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000505

AC:

732

AN:

1450276

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

350

AN XY:

720710

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.0000919

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000189

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.000614

Gnomad4 OTH exome

AF:

0.000435

GnomAD4 genome

AF:

0.000276

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000136

Hom.:

1124

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ExAC

AF:

0.000199

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;D;.;.

Eigen

Benign

-0.0024

Eigen_PC

Benign

0.073

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.86

.;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.;.

MutationTaster

Benign

0.86

D;D;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.3

D;D;N;D

REVEL

Benign

0.21

Sift

Benign

0.10

T;T;T;D

Sift4G

Benign

0.16

T;T;D;T

Polyphen

0.65

P;P;P;P

Vest4

0.45

MVP

0.62

MPC

0.40

ClinPred

0.15

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.47

dbscSNV1_RF

Benign

0.40

SpliceAI score (max)

0.18

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