rs28460440

chrX-1303975-G-AchrX-1303975-G-T

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.999G>A(p.Val333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,611,098 control chromosomes in the GnomAD database, including 130,600 homozygotes. There are 318,614 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. V333V) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.37 (10490 hom., 26891 hem., cov: 28)
  • Exomes 𝑓: 0.40 (120110 hom. 291723 hem.)
• Consequence: CSF2RA NM_172245.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 0.337

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=-0.88).
• BP6: Variant X-1303975-G-A is Benign according to our data. Variant chrX-1303975-G-A is described in ClinVar as [Benign]. Clinvar id is 178717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.337 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.999G>A	p.Val333=	synonymous_variant	11/13	ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.999G>A	p.Val333=	synonymous_variant	11/13	1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55455 AN: 150282 Hom.: 10486 Cov.: 28 AF XY: 0.367 AC XY: 26873 AN XY: 73154

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.385

GnomAD3 exomes AF: 0.373 AC: 93680 AN: 251110 Hom.: 17961 AF XY: 0.376 AC XY: 51008 AN XY: 135690

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.355

Gnomad SAS exome AF: 0.319

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.412

Gnomad OTH exome AF: 0.388

GnomAD4 exome AF: 0.403 AC: 588155 AN: 1460694 Hom.: 120110 Cov.: 48 AF XY: 0.402 AC XY: 291723 AN XY: 726492

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.369 AC: 55464 AN: 150404 Hom.: 10490 Cov.: 28 AF XY: 0.367 AC XY: 26891 AN XY: 73284

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.382

Bravo AF: 0.362

EpiCase AF: 0.425

EpiControl AF: 0.426

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

Val333Val in exon 12 of CSF2RA: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 43.0% (3695/8592) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs146020675). -

Surfactant metabolism dysfunction, pulmonary, 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.64
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28460440; hg19: chrX-1422868; COSMIC: COSV62625891; COSMIC: COSV62625891;