rs3918018

Positions:

chr1-36472277-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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:3

Conservation

PhyloP100: -0.123

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:

CSF3R (HGNC:):

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=0.005912125).

BP6

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

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3R	NM_000760.4 linkuse as main transcript	c.958G>A	p.Asp320Asn	missense_variant	8/17	ENST00000373106.6	NP_000751.1	Q99062-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6 linkuse as main transcript	c.958G>A	p.Asp320Asn	missense_variant	8/17	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

GnomAD3 exomes

AF:

0.0188

AC:

4725

AN:

251056

Hom.:

AF XY:

0.0187

AC XY:

2541

AN XY:

135854

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 SAS exome

AF:

0.00284

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

Gnomad4 AFR exome

AF:

0.00469

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.0205

Gnomad4 NFE exome

AF:

0.0304

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0204

AC:

3111

AN:

152256

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1483

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00623

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0213

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0266

Hom.:

116

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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

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

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