rs3917981

Variant summary

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

The NM_000760.4(CSF3R):c.1260T>C(p.Thr420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,613,338 control chromosomes in the GnomAD database, including 255,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27479 hom., cov: 33)

Exomes 𝑓: 0.56 ( 228059 hom. )

Consequence

CSF3R
NM_000760.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.764

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-36471458-A-G is Benign according to our data. Variant chr1-36471458-A-G is described in ClinVar as [Benign]. Clinvar id is 256790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-36471458-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.764 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF3R	NM_000760.4 linkuse as main transcript	c.1260T>C	p.Thr420=	synonymous_variant	10/17	ENST00000373106.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF3R	ENST00000373106.6 linkuse as main transcript	c.1260T>C	p.Thr420=	synonymous_variant	10/17	1	NM_000760.4	P1	Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90384

AN:

151902

Hom.:

27455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.554

AC:

139121

AN:

251314

Hom.:

39914

AF XY:

0.565

AC XY:

76716

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.545

Gnomad EAS exome

AF:

0.408

Gnomad SAS exome

AF:

0.684

Gnomad FIN exome

AF:

0.606

Gnomad NFE exome

AF:

0.555

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.555

AC:

811310

AN:

1461316

Hom.:

228059

Cov.:

AF XY:

0.560

AC XY:

406743

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.550

Gnomad4 EAS exome

AF:

0.428

Gnomad4 SAS exome

AF:

0.685

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.595

AC:

90456

AN:

152022

Hom.:

27479

Cov.:

AF XY:

0.598

AC XY:

44414

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.615

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.589

Alfa

AF:

0.565

Hom.:

29326

Bravo

AF:

0.583

Asia WGS

AF:

0.579

AC:

2011

AN:

3478

EpiCase

AF:

0.562

EpiControl

AF:

0.563

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

Cadd

Benign

0.37

Dann

Benign

0.32

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