1-36469668-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_000760.4(CSF3R):​c.1458G>A​(p.Thr486Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

CSF3R
NM_000760.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06
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 -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 1-36469668-C-T is Benign according to our data. Variant chr1-36469668-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.06 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00143 (218/152354) while in subpopulation AFR AF= 0.00471 (196/41582). AF 95% confidence interval is 0.00417. There are 0 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSF3RNM_000760.4 linkc.1458G>A p.Thr486Thr synonymous_variant Exon 11 of 17 ENST00000373106.6 NP_000751.1 Q99062-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSF3RENST00000373106.6 linkc.1458G>A p.Thr486Thr synonymous_variant Exon 11 of 17 1 NM_000760.4 ENSP00000362198.2 Q99062-1

Frequencies

GnomAD3 genomes
AF:
0.00144
AC:
219
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00475
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000453
AC:
114
AN:
251398
Hom.:
0
AF XY:
0.000353
AC XY:
48
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00418
Gnomad AMR exome
AF:
0.000954
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000791
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000205
AC:
299
AN:
1461794
Hom.:
0
Cov.:
32
AF XY:
0.000184
AC XY:
134
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00406
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000818
Gnomad4 OTH exome
AF:
0.000480
GnomAD4 genome
AF:
0.00143
AC:
218
AN:
152354
Hom.:
0
Cov.:
33
AF XY:
0.00109
AC XY:
81
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00471
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000589
Hom.:
0
Bravo
AF:
0.00150
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 19, 2017
Genetic Services Laboratory, University of Chicago
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency Benign:1
Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.46
DANN
Benign
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs138289951; hg19: chr1-36935269; API