dbSNP rs3917979: CSF3R:c.1072-145A>G (chr1-36471791-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000760.4(CSF3R):c.1072-145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 810,694 control chromosomes in the GnomAD database, including 18,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4245 hom., cov: 32)

Exomes 𝑓: 0.20 ( 14413 hom. )

Consequence

CSF3R
NM_000760.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.822

Publications

5 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 (BayesDel_noAF=-0.85).

BP6

Variant 1-36471791-T-C is Benign according to our data. Variant chr1-36471791-T-C is described in ClinVar as [Benign]. Clinvar id is 1181291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4 link	c.1072-145A>G		intron_variant	Intron 9 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.1072-145A>G		intron_variant	Intron 9 of 16	1	NM_000760.4	ENSP00000362198.2		Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34555

AN:

151862

Hom.:

4239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.202

AC:

133190

AN:

658714

Hom.:

14413

Cov.:

AF XY:

0.206

AC XY:

70322

AN XY:

342004

show subpopulations

African (AFR)

AF:

0.311

AC:

5186

AN:

16682

American (AMR)

AF:

0.131

AC:

3386

AN:

25884

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

2541

AN:

16302

East Asian (EAS)

AF:

0.293

AC:

9519

AN:

32458

South Asian (SAS)

AF:

0.271

AC:

14799

AN:

54574

European-Finnish (FIN)

AF:

0.197

AC:

7218

AN:

36646

Middle Eastern (MID)

AF:

0.194

AC:

470

AN:

2420

European-Non Finnish (NFE)

AF:

0.188

AC:

83042

AN:

440706

Other (OTH)

AF:

0.213

AC:

7029

AN:

33042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6145

12291

18436

24582

30727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1698

3396

5094

6792

8490

<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:

0.228

AC:

34589

AN:

151980

Hom.:

4245

Cov.:

AF XY:

0.231

AC XY:

17143

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.312

AC:

12905

AN:

41424

American (AMR)

AF:

0.177

AC:

2700

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

529

AN:

3466

East Asian (EAS)

AF:

0.247

AC:

1269

AN:

5146

South Asian (SAS)

AF:

0.277

AC:

1336

AN:

4822

European-Finnish (FIN)

AF:

0.209

AC:

2209

AN:

10578

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13074

AN:

67948

Other (OTH)

AF:

0.234

AC:

492

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1356

2713

4069

5426

6782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.201

Hom.:

5191

Bravo

AF:

0.224

Asia WGS

AF:

0.292

AC:

1012

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 11, 2021

GeneDx

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

-0.85

CADD

Benign

0.69

(source)

DANN

Benign

0.81

PhyloP100

-0.82

PromoterAI

0.0091

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