NM_000760.4:c.958G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000760.4(CSF3R):c.958G>A(p.Asp320Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 1,614,142 control chromosomes in the GnomAD database, including 624 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 39 hom., cov: 32)

Exomes 𝑓: 0.026 ( 585 hom. )

Consequence

CSF3R
NM_000760.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.123

Publications

21 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005912125).

BP6

Variant 1-36472277-C-T is Benign according to our data. Variant chr1-36472277-C-T is described in ClinVar as Benign. ClinVar VariationId is 256796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0204 (3111/152256) while in subpopulation NFE AF = 0.0323 (2194/68012). AF 95% confidence interval is 0.0311. There are 39 homozygotes in GnomAd4. There are 1483 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4 link	c.958G>A	p.Asp320Asn	missense_variant	Exon 8 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.958G>A	p.Asp320Asn	missense_variant	Exon 8 of 17	1	NM_000760.4	ENSP00000362198.2		Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3113

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00628

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0188

AC:

4725

AN:

251056

AF XY:

0.0187

show subpopulations

Gnomad AFR exome

AF:

0.00505

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0222

GnomAD4 exome

AF:

0.0262

AC:

38243

AN:

1461886

Hom.:

585

Cov.:

AF XY:

0.0256

AC XY:

18615

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00469

AC:

157

AN:

33480

American (AMR)

AF:

0.0144

AC:

645

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

647

AN:

26136

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.00260

AC:

224

AN:

86254

European-Finnish (FIN)

AF:

0.0205

AC:

1097

AN:

53418

Middle Eastern (MID)

AF:

0.0281

AC:

162

AN:

5768

European-Non Finnish (NFE)

AF:

0.0304

AC:

33849

AN:

1112010

Other (OTH)

AF:

0.0240

AC:

1449

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2358

4716

7073

9431

11789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1262

2524

3786

5048

6310

<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:

0.0204

AC:

3111

AN:

152256

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1483

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00623

AC:

259

AN:

41554

American (AMR)

AF:

0.0171

AC:

262

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3472

East Asian (EAS)

AF:

0.000582

AC:

AN:

5158

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0213

AC:

226

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0323

AC:

2194

AN:

68012

Other (OTH)

AF:

0.0180

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0252

Hom.:

196

Bravo

AF:

0.0194

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.0306

AC:

263

ExAC

AF:

0.0189

AC:

2297

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0283

EpiControl

AF:

0.0261

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 27, 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

- -

not specified

Benign:1

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:1

Feb 02, 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

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.7

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.17

T;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.41

.;.;T;T;T

MetaRNN

Benign

0.0059

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.57

N;N;N;N;N

PhyloP100

-0.12

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

N;N;N;N;N

REVEL

Benign

0.091

Sift

Benign

0.39

T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.038

MPC

0.28

ClinPred

0.0051

GERP RS

-5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.28

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