Genetic Variant CSF3R:n.1610C>T (chr1-36480052-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000489551.6(CSF3R):n.1610C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 204,150 control chromosomes in the GnomAD database, including 12,931 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 9243 hom., cov: 32)

Exomes 𝑓: 0.37 ( 3688 hom. )

Consequence

CSF3R
ENST00000489551.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.633

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4 link	c.-20-536C>T		intron_variant	Intron 2 of 16	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.-20-536C>T		intron_variant	Intron 2 of 16	1	NM_000760.4	ENSP00000362198.2		Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50341

AN:

151982

Hom.:

9243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.404

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.383

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.365

AC:

19019

AN:

52050

Hom.:

3688

Cov.:

AF XY:

0.370

AC XY:

10133

AN XY:

27402

show subpopulations

African (AFR)

AF:

0.187

AC:

359

AN:

1918

American (AMR)

AF:

0.479

AC:

1794

AN:

3742

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

437

AN:

1104

East Asian (EAS)

AF:

0.0999

AC:

342

AN:

3422

South Asian (SAS)

AF:

0.435

AC:

3407

AN:

7836

European-Finnish (FIN)

AF:

0.383

AC:

627

AN:

1638

Middle Eastern (MID)

AF:

0.399

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.373

AC:

11108

AN:

29778

Other (OTH)

AF:

0.360

AC:

890

AN:

2474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

527

1053

1580

2106

2633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<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:

0.331

AC:

50355

AN:

152100

Hom.:

9243

Cov.:

AF XY:

0.333

AC XY:

24797

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.188

AC:

7788

AN:

41520

American (AMR)

AF:

0.449

AC:

6858

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1401

AN:

3470

East Asian (EAS)

AF:

0.119

AC:

617

AN:

5182

South Asian (SAS)

AF:

0.445

AC:

2147

AN:

4828

European-Finnish (FIN)

AF:

0.383

AC:

4045

AN:

10574

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.388

AC:

26335

AN:

67926

Other (OTH)

AF:

0.333

AC:

703

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1672

3344

5016

6688

8360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.377

Hom.:

21875

Bravo

AF:

0.325

Asia WGS

AF:

0.262

AC:

912

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

(source)

DANN

Benign

0.69

PhyloP100

0.63

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over