X-1309528-G-T

Position:

chrX-1309528-G-T

Variant summary

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

The NM_172246.4(CSF2RA):c.1073G>T(p.Arg358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,613,540 control chromosomes in the GnomAD database, including 10,306 homozygotes. There are 71,282 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2542 hom., 10929 hem., cov: 33)

Exomes 𝑓: 0.078 ( 7764 hom. 60353 hem. )

Consequence

CSF2RA
NM_172246.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.816

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=0.0031292737).

BP6

Variant X-1309528-G-T is Benign according to our data. Variant chrX-1309528-G-T is described in ClinVar as [Benign]. Clinvar id is 226543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 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.*49G>T		3_prime_UTR_variant	13/13	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.*49G>T		3_prime_UTR_variant	13/13	1	NM_172245.4	ENSP00000370940.3		P15509-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21955

AN:

152040

Hom.:

2527

Cov.:

AF XY:

0.147

AC XY:

10885

AN XY:

74270

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.0787

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0561

Gnomad OTH

AF:

0.138

GnomAD3 exomes

AF:

0.113

AC:

28443

AN:

251160

Hom.:

2628

AF XY:

0.116

AC XY:

15770

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0998

Gnomad ASJ exome

AF:

0.0448

Gnomad EAS exome

AF:

0.138

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.0711

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0964

GnomAD4 exome

AF:

0.0780

AC:

113991

AN:

1461382

Hom.:

7764

Cov.:

AF XY:

0.0830

AC XY:

60353

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.261

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.0534

Gnomad4 OTH exome

AF:

0.0982

GnomAD4 genome

AF:

0.145

AC:

22006

AN:

152158

Hom.:

2542

Cov.:

AF XY:

0.147

AC XY:

10929

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.0787

Gnomad4 NFE

AF:

0.0561

Gnomad4 OTH

AF:

0.138

Bravo

AF:

0.149

TwinsUK

AF:

0.0561

AC:

208

ALSPAC

AF:

0.0503

AC:

194

ESP6500AA

AF:

0.300

AC:

1324

ESP6500EA

AF:

0.0556

AC:

478

ExAC

AF:

0.120

AC:

14550

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Feb 06, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 26, 2014

p.Arg358Leu in exon 11 of CSF2RA: This variant is not expected to have clinical significance because it has been identified in 30% (1324/4406) of African Americ an chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/; dbSNP rs28722602). -

CSF2RA-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2020

This variant is classified as likely 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

-0.99

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.59

DANN

Benign

0.13

FATHMM_MKL

Benign

0.00028

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.97

PROVEAN

Benign

2.1

REVEL

Benign

0.042

Sift

Pathogenic

0.0

Vest4

0.24

ClinPred

0.0024

GERP RS

-0.69

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