rs3918001

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

1
1
13

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]

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
CSF3RNM_000760.4 linkuse as main transcriptc.2041-75G>A intron_variant ENST00000373106.6 NP_000751.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSF3RENST00000373106.6 linkuse as main transcriptc.2041-75G>A intron_variant 1 NM_000760.4 ENSP00000362198 P1Q99062-1

Frequencies

GnomAD3 genomes
AF:
0.0443
AC:
6741
AN:
152154
Hom.:
483
Cov.:
33
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.:
31
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.:
33
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:
7
ALSPAC
AF:
0.00182
AC:
7
ESP6500AA
AF:
0.140
AC:
616
ESP6500EA
AF:
0.00128
AC:
11
ExAC
AF:
0.0149
AC:
1810
Asia WGS
AF:
0.0110
AC:
38
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 submitterclinical testingGeneDxMay 11, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.79
T
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
N
LIST_S2
Benign
0.33
T
MetaRNN
Benign
0.0014
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
P;P;P;P;P;P;P;P
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.035
Sift
Benign
0.42
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.0040
B
Vest4
0.046
MutPred
0.23
Loss of sheet (P = 0.0126);
MPC
0.39
ClinPred
0.0074
T
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.

Other links and lift over

dbSNP: rs3918001; hg19: chr1-36932503; API