Variant 1-109923913-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 ENST00000329608.11(CSF1):c.1292C>T(p.Ser431Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,613,982 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00032 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

CSF1
ENST00000329608.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.830

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=0.038914412).

BS2

High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.1292C>T	p.Ser431Leu	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.1292C>T	p.Ser431Leu	missense_variant	6/9	1	NM_000757.6	ENSP00000327513.6	P09603-1
CSF1	ENST00000369802.7 linkuse as main transcript	c.1292C>T	p.Ser431Leu	missense_variant	6/9	1		ENSP00000358817.3	P09603-1
CSF1	ENST00000369801.1 linkuse as main transcript	c.1091-147C>T		intron_variant		1		ENSP00000358816.1	P09603-2
CSF1	ENST00000420111.6 linkuse as main transcript	c.545-147C>T		intron_variant		5		ENSP00000407317.2	P09603-3

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000603

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000323

AC:

AN:

250640

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000654

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000480

AC:

702

AN:

1461738

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

335

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000601

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000315

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000371

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000237

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

Oct 12, 2022

The c.1292C>T (p.S431L) 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 1292, causing the serine (S) at amino acid position 431 to be replaced by a leucine (L). 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

0.078

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.059

Sift

Benign

0.19

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.029

B;B

Vest4

0.21

MVP

0.16

MPC

0.097

ClinPred

0.025

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.057

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