Variant rs3917998 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000760.4(CSF3R):c.1794C>T(p.Ile598=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,246 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 15 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

CSF3R
NM_000760.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.138

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:

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 (BayesDel_noAF=-0.57).

BP6

Variant 1-36467892-G-A is Benign according to our data. Variant chr1-36467892-G-A is described in ClinVar as [Benign]. Clinvar id is 434835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00799 (1217/152354) while in subpopulation AFR AF= 0.0276 (1146/41586). AF 95% confidence interval is 0.0262. There are 15 homozygotes in gnomad4. There are 535 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3R	NM_000760.4 linkuse as main transcript	c.1794C>T	p.Ile598=	synonymous_variant	14/17	ENST00000373106.6	NP_000751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6 linkuse as main transcript	c.1794C>T	p.Ile598=	synonymous_variant	14/17	1	NM_000760.4	ENSP00000362198	P1	Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.00801

AC:

1220

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00243

AC:

612

AN:

251466

Hom.:

AF XY:

0.00179

AC XY:

243

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00103

AC:

1513

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

674

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00799

AC:

1217

AN:

152354

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

535

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.00937

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000533

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

Genetic Services Laboratory, University of Chicago

Mar 07, 2017

- -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 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

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.8

DANN

Benign

0.56

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