Variant rs3918017 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000373106.6(CSF3R):c.726C>T(p.Ala242=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,611,898 control chromosomes in the GnomAD database, including 290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 23 hom., cov: 32)

Exomes 𝑓: 0.016 ( 267 hom. )

Consequence

CSF3R
ENST00000373106.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.264

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=-0.86).

BP6

Variant 1-36472634-G-A is Benign according to our data. Variant chr1-36472634-G-A is described in ClinVar as [Benign]. Clinvar id is 256795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-36472634-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.264 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0131 (2001/152294) while in subpopulation AMR AF= 0.0235 (360/15304). AF 95% confidence interval is 0.0215. There are 23 homozygotes in gnomad4. There are 952 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3R	NM_000760.4 linkuse as main transcript	c.726C>T	p.Ala242=	synonymous_variant	7/17	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.726C>T	p.Ala242=	synonymous_variant	7/17	1	NM_000760.4	ENSP00000362198	P1	Q99062-1

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2002

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0248

GnomAD3 exomes

AF:

0.0131

AC:

3224

AN:

245884

Hom.:

AF XY:

0.0133

AC XY:

1789

AN XY:

134156

show subpopulations

Gnomad AFR exome

AF:

0.00270

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.00666

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00321

Gnomad FIN exome

AF:

0.00592

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0193

GnomAD4 exome

AF:

0.0162

AC:

23658

AN:

1459604

Hom.:

267

Cov.:

AF XY:

0.0161

AC XY:

11693

AN XY:

725794

show subpopulations

Gnomad4 AFR exome

AF:

0.00302

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.00644

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00377

Gnomad4 FIN exome

AF:

0.00634

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0131

AC:

2001

AN:

152294

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

952

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00791

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0162

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0224

EpiControl

AF:

0.0255

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

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive severe congenital neutropenia due to CSF3R deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 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

-0.86

CADD

Benign

2.7

DANN

Benign

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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