rs28460440

Variant names:

• chrX-1303975-G-A
• rs28460440
• NM_172245.4:c.999G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-1303975-G-A
• chrX-1303975-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_172245.4(CSF2RA):​c.999G>A​(p.Val333Val) 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:4 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CSF2RA	NM_172245.4	c.999G>A	p.Val333Val	synonymous_variant	Exon 11 of 13	ENST00000381529.9	NP_758448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9	c.999G>A	p.Val333Val	synonymous_variant	Exon 11 of 13	1	NM_172245.4	ENSP00000370940.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55455 AN: 150282 Hom.: 10486 Cov.: 28

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

GnomAD2 exomes AF: 0.373 AC: 93680 AN: 251110 AF XY: 0.376

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 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 AC: 9530 AN: 33446

Gnomad4 AMR exome AF: 0.303 AC: 13536 AN: 44712

Gnomad4 ASJ exome AF: 0.373 AC: 9734 AN: 26106

Gnomad4 EAS exome AF: 0.295 AC: 11690 AN: 39692

Gnomad4 SAS exome AF: 0.328 AC: 28264 AN: 86214

Gnomad4 FIN exome AF: 0.438 AC: 23411 AN: 53406

Gnomad4 NFE exome AF: 0.419 AC: 466032 AN: 1111022

Gnomad4 Remaining exome AF: 0.393 AC: 23715 AN: 60338

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 AC: 0.287256 AN: 0.287256

Gnomad4 AMR AF: 0.333 AC: 0.332912 AN: 0.332912

Gnomad4 ASJ AF: 0.381 AC: 0.380939 AN: 0.380939

Gnomad4 EAS AF: 0.334 AC: 0.333731 AN: 0.333731

Gnomad4 SAS AF: 0.312 AC: 0.311631 AN: 0.311631

Gnomad4 FIN AF: 0.444 AC: 0.444026 AN: 0.444026

Gnomad4 NFE AF: 0.419 AC: 0.419012 AN: 0.419012

Gnomad4 OTH AF: 0.382 AC: 0.381528 AN: 0.381528

Bravo AF: 0.362

EpiCase AF: 0.425

EpiControl AF: 0.426

ClinVar

Significance: Benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

Dec 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

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

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;