Variant 1-109923252-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.631C>T(p.Leu211Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,604,738 control chromosomes in the GnomAD database, including 3 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 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

CSF1
ENST00000329608.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.352

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=0.014556259).

BS2

High AC in GnomAd4 at 114 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF1	NM_000757.6 linkuse as main transcript	c.631C>T	p.Leu211Phe	missense_variant	6/9	ENST00000329608.11	NP_000748.4	P09603-1A0A024R0A1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11 linkuse as main transcript	c.631C>T	p.Leu211Phe	missense_variant	6/9	1	NM_000757.6	ENSP00000327513.6		P09603-1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000573

AC:

139

AN:

242532

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

130648

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000417

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00117

AC:

1701

AN:

1452440

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

863

AN XY:

721794

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.000504

Gnomad4 ASJ exome

AF:

0.0000792

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.000967

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152298

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000675

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

Sep 27, 2021

The c.631C>T (p.L211F) 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 631, causing the leucine (L) at amino acid position 211 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;T;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.81

.;T;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;L;L

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.16

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.059

B;.;B;B

Vest4

0.054

MVP

0.34

MPC

0.17

ClinPred

0.016

GERP RS

3.7

Varity_R

0.071

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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