rs67006588

Positions:

chrX-1282753-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172245.4(CSF2RA):c.50C>G(p.Ala17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 1,613,236 control chromosomes in the GnomAD database, including 15,059 homozygotes. There are 50,831 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 7352 hom., 13897 hem., cov: 31)

Exomes 𝑓: 0.053 ( 7707 hom. 36934 hem. )

Consequence

CSF2RA
NM_172245.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0340

Variant links:

Genes affected

CSF2RA (HGNC:2435): (colony stimulating factor 2 receptor subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages. The encoded protein is a member of the cytokine family of receptors. This gene is found in the pseudoautosomal region (PAR) of the X and Y chromosomes. Multiple transcript variants encoding different isoforms have been found for this gene, with some of the isoforms being membrane-bound and others being soluble. [provided by RefSeq, Jul 2008]

CSF2RA links:

CSF2RA (HGNC:):

CSF2RA 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 (MetaRNN=2.9688486E-5).

BP6

Variant X-1282753-C-G is Benign according to our data. Variant chrX-1282753-C-G is described in ClinVar as [Benign]. Clinvar id is 178714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RA	NM_172245.4 linkuse as main transcript	c.50C>G	p.Ala17Gly	missense_variant	3/13	ENST00000381529.9	NP_758448.1	P15509-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9 linkuse as main transcript	c.50C>G	p.Ala17Gly	missense_variant	3/13	1	NM_172245.4	ENSP00000370940.3		P15509-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29461

AN:

151968

Hom.:

7334

Cov.:

AF XY:

0.187

AC XY:

13853

AN XY:

74228

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0296

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.0782

AC:

19629

AN:

251158

Hom.:

3180

AF XY:

0.0669

AC XY:

9075

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0337

Gnomad EAS exome

AF:

0.0280

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0667

GnomAD4 exome

AF:

0.0531

AC:

77589

AN:

1461150

Hom.:

7707

Cov.:

AF XY:

0.0508

AC XY:

36934

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.602

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.0340

Gnomad4 EAS exome

AF:

0.0201

Gnomad4 SAS exome

AF:

0.0400

Gnomad4 FIN exome

AF:

0.0389

Gnomad4 NFE exome

AF:

0.0382

Gnomad4 OTH exome

AF:

0.0761

GnomAD4 genome

AF:

0.194

AC:

29513

AN:

152086

Hom.:

7352

Cov.:

AF XY:

0.187

AC XY:

13897

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.585

Gnomad4 AMR

AF:

0.0909

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.0295

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.0336

Gnomad4 NFE

AF:

0.0393

Gnomad4 OTH

AF:

0.155

Bravo

AF:

0.215

TwinsUK

AF:

0.0353

AC:

131

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.575

AC:

2532

ESP6500EA

AF:

0.0417

AC:

358

ExAC

AF:

0.0884

AC:

10735

EpiCase

AF:

0.0413

EpiControl

AF:

0.0408

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Ala17Gly in exon 4 of CSF2RA: This variant is not expected to have clinical sign ificance because it has been identified in 42.5% (1874/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs142270234). -

Surfactant metabolism dysfunction, pulmonary, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

CSF2RA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.21

T;.;T;T;T;.;T;.;.;.

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.59

.;T;.;T;T;T;T;T;T;T

MetaRNN

Benign

0.000030

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;L;.;L;L;.;L;L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N;N;N;N;N;.;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.11

T;T;T;T;T;T;.;T;D;T

Sift4G

Uncertain

0.032

D;D;D;D;D;D;D;D;D;D

Polyphen

0.95

P;.;P;.;P;D;.;D;D;D

Vest4

0.16

MPC

0.33

ClinPred

0.014

GERP RS

0.19

Varity_R

0.077

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