rs3917980

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000760.4(CSF3R):c.1254T>C(p.Arg418Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,654 control chromosomes in the GnomAD database, including 90,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6838 hom., cov: 33)

Exomes 𝑓: 0.33 ( 83836 hom. )

Consequence

CSF3R
NM_000760.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.68

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

hereditary neutrophilia
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
autosomal recessive severe congenital neutropenia due to CSF3R deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

CSF3R links:

ENSG00000297367 (HGNC:):

ENSG00000297367 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.008).

BP6

Variant 1-36471464-A-G is Benign according to our data. Variant chr1-36471464-A-G is described in ClinVar as Benign. ClinVar VariationId is 256789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4 link	c.1254T>C	p.Arg418Arg	synonymous_variant	Exon 10 of 17	ENST00000373106.6	NP_000751.1	Q99062-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6 link	c.1254T>C	p.Arg418Arg	synonymous_variant	Exon 10 of 17	1	NM_000760.4	ENSP00000362198.2		Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43964

AN:

151966

Hom.:

6844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.313

AC:

78552

AN:

251318

AF XY:

0.324

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.333

AC:

487263

AN:

1461568

Hom.:

83836

Cov.:

AF XY:

0.336

AC XY:

244659

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.189

AC:

6335

AN:

33476

American (AMR)

AF:

0.255

AC:

11399

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9510

AN:

26136

East Asian (EAS)

AF:

0.0837

AC:

3321

AN:

39698

South Asian (SAS)

AF:

0.407

AC:

35089

AN:

86250

European-Finnish (FIN)

AF:

0.345

AC:

18415

AN:

53414

Middle Eastern (MID)

AF:

0.355

AC:

2044

AN:

5754

European-Non Finnish (NFE)

AF:

0.344

AC:

382139

AN:

1111740

Other (OTH)

AF:

0.315

AC:

19011

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18869

37738

56607

75476

94345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12168

24336

36504

48672

60840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.289

AC:

43949

AN:

152086

Hom.:

6838

Cov.:

AF XY:

0.288

AC XY:

21420

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.197

AC:

8179

AN:

41524

American (AMR)

AF:

0.268

AC:

4094

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1285

AN:

3468

East Asian (EAS)

AF:

0.115

AC:

596

AN:

5164

South Asian (SAS)

AF:

0.396

AC:

1912

AN:

4824

European-Finnish (FIN)

AF:

0.338

AC:

3575

AN:

10570

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23064

AN:

67936

Other (OTH)

AF:

0.285

AC:

601

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1627

3254

4880

6507

8134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

12907

Bravo

AF:

0.277

Asia WGS

AF:

0.229

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 22, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.13

(source)

DANN

Benign

0.53

PhyloP100

-2.7

PromoterAI

-0.0031

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over