Variant 1-36466902-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000373103.5(CSF3R):c.2047G>A(p.Gly683Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00906 in 1,613,922 control chromosomes in the GnomAD database, including 910 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 485 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 425 hom. )

Consequence

CSF3R
ENST00000373103.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.797

Variant links:

Genes affected

CSF3R (HGNC:2439): (colony stimulating factor 3 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 3, a cytokine that controls the production, differentiation, and function of granulocytes. The encoded protein, which is a member of the family of cytokine receptors, may also function in some cell surface adhesion or recognition processes. Alternatively spliced transcript variants have been described. Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia. [provided by RefSeq, Aug 2010]

CSF3R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013715625).

BP6

Variant 1-36466902-C-T is Benign according to our data. Variant chr1-36466902-C-T is described in ClinVar as [Benign]. Clinvar id is 262792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3R	NM_000760.4 linkuse as main transcript	c.2041-75G>A		intron_variant		ENST00000373106.6	NP_000751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6 linkuse as main transcript	c.2041-75G>A		intron_variant		1	NM_000760.4	ENSP00000362198	P1	Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6741

AN:

152154

Hom.:

483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00196

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0120

AC:

2944

AN:

245468

Hom.:

182

AF XY:

0.00930

AC XY:

1245

AN XY:

133820

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.00834

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000931

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00845

GnomAD4 exome

AF:

0.00537

AC:

7856

AN:

1461650

Hom.:

425

Cov.:

AF XY:

0.00479

AC XY:

3483

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0444

AC:

6763

AN:

152272

Hom.:

485

Cov.:

AF XY:

0.0432

AC XY:

3220

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0174

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00196

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.00846

Hom.:

180

Bravo

AF:

0.0499

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.140

AC:

616

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0149

AC:

1810

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.85

DANN

Uncertain

0.99

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.22

REVEL

Benign

0.035

Sift

Benign

0.42

Sift4G

Pathogenic

0.0

Polyphen

0.0040

Vest4

0.046

MutPred

0.23

Loss of sheet (P = 0.0126);

MPC

0.39

ClinPred

0.0074

GERP RS

-2.7

gMVP

0.30

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