Variant rs3917980 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000760.4(CSF3R):c.1254T>C(p.Arg418Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,654 control chromosomes in the GnomAD database, including 90,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6838 hom., cov: 33)

Exomes 𝑓: 0.33 ( 83836 hom. )

Consequence

CSF3R
NM_000760.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.68

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-36471464-A-G is Benign according to our data. Variant chr1-36471464-A-G is described in ClinVar as [Benign]. Clinvar id is 256789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3R	NM_000760.4 linkuse as main transcript	c.1254T>C	p.Arg418Arg	synonymous_variant	10/17	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.1254T>C	p.Arg418Arg	synonymous_variant	10/17	1	NM_000760.4	ENSP00000362198.2		Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43964

AN:

151966

Hom.:

6844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.313

AC:

78552

AN:

251318

Hom.:

13268

AF XY:

0.324

AC XY:

44049

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.333

AC:

487263

AN:

1461568

Hom.:

83836

Cov.:

AF XY:

0.336

AC XY:

244659

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.0837

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.289

AC:

43949

AN:

152086

Hom.:

6838

Cov.:

AF XY:

0.288

AC XY:

21420

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.339

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.329

Hom.:

10806

Bravo

AF:

0.277

Asia WGS

AF:

0.229

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 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

-0.91

CADD

Benign

0.13

DANN

Benign

0.53

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