X-1309528-G-A

Position:

chrX-1309528-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000355432.8(CSF2RA):c.1073G>A(p.Arg358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,780 control chromosomes in the GnomAD database, including 195 homozygotes. There are 10,195 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R358L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0091 ( 9 hom., 703 hem., cov: 33)

Exomes 𝑓: 0.012 ( 186 hom. 9492 hem. )

Consequence

CSF2RA
ENST00000355432.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028986335).

BP6

Variant X-1309528-G-A is Benign according to our data. Variant chrX-1309528-G-A is described in ClinVar as [Benign]. Clinvar id is 3036043.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00915 (1392/152192) while in subpopulation SAS AF= 0.0324 (156/4822). AF 95% confidence interval is 0.0282. There are 9 homozygotes in gnomad4. There are 703 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RA	NM_172245.4 linkuse as main transcript	c.*49G>A		3_prime_UTR_variant	13/13	ENST00000381529.9	NP_758448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9 linkuse as main transcript	c.*49G>A		3_prime_UTR_variant	13/13	1	NM_172245.4	ENSP00000370940	A2	P15509-1

Frequencies

GnomAD3 genomes

AF:

0.00916

AC:

1393

AN:

152074

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

703

AN XY:

74292

show subpopulations

Gnomad AFR

AF:

0.00242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0116

AC:

2901

AN:

251160

Hom.:

AF XY:

0.0131

AC XY:

1778

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00581

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.00924

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0124

AC:

18193

AN:

1461588

Hom.:

186

Cov.:

AF XY:

0.0131

AC XY:

9492

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0302

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00915

AC:

1392

AN:

152192

Hom.:

Cov.:

AF XY:

0.00945

AC XY:

703

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0324

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.00947

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0135

AC:

ExAC

AF:

0.0121

AC:

1475

EpiCase

AF:

0.00987

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 01, 2022

p.Arg358Gln in exon 11 of CSF2RA: This variant is not expected to have clinical significance because it has been identified in 3% (927/30780) of South Asian chromosomes, including 17 homozygotes and 1.2% (1538/128868) of European chromosomes, including 13 homozygotes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1; BP4. -

CSF2RA-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2022

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

-0.90

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.71

DANN

Benign

0.69

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PROVEAN

Benign

0.21

REVEL

Benign

0.019

Sift

Pathogenic

0.0

Vest4

0.12

ClinPred

0.0082

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