rs73618036

chrX-1290424-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_172245.4(CSF2RA):c.561G>A(p.Thr187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,613,688 control chromosomes in the GnomAD database, including 318 homozygotes. There are 3,724 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T187T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.027 (179 hom., 1880 hem., cov: 32)
  • Exomes 𝑓: 0.0028 (139 hom. 1844 hem.)
• Consequence: CSF2RA NM_172245.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.72

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-1290424-G-A is Benign according to our data. Variant chrX-1290424-G-A is described in ClinVar as [Benign]. Clinvar id is 178716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.561G>A	p.Thr187=	synonymous_variant	7/13	ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.561G>A	p.Thr187=	synonymous_variant	7/13	1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4047 AN: 152016 Hom.: 178 Cov.: 32 AF XY: 0.0253 AC XY: 1875 AN XY: 74242

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00666 AC: 1674 AN: 251174 Hom.: 74 AF XY: 0.00503 AC XY: 683 AN XY: 135738

Gnomad AFR exome AF: 0.0888

Gnomad AMR exome AF: 0.00477

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00283 AC: 4133 AN: 1461556 Hom.: 139 Cov.: 32 AF XY: 0.00254 AC XY: 1844 AN XY: 727078

Gnomad4 AFR exome AF: 0.0942

Gnomad4 AMR exome AF: 0.00581

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000248

Gnomad4 OTH exome AF: 0.00624

GnomAD4 genome AF: 0.0267 AC: 4055 AN: 152132 Hom.: 179 Cov.: 32 AF XY: 0.0253 AC XY: 1880 AN XY: 74368

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0128

Bravo AF: 0.0300

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Thr187Thr in exon 8 of CSF2RA: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 8.9% (390/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs149374461). -

Surfactant metabolism dysfunction, pulmonary, 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 18, 2019

- -

CSF2RA-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 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_noAF	Benign	-0.89
Cadd	Benign	0.050
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs73618036; hg19: chrX-1409317;