rs28460440

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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 (★★).

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.337

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:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
CSF2RA	NM_172245.4 linkuse as main transcript	c.999G>A	p.Val333Val	synonymous_variant	11/13	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.999G>A	p.Val333Val	synonymous_variant	11/13	1	NM_172245.4	ENSP00000370940.3		P15509-1

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55455

AN:

150282

Hom.:

10486

Cov.:

AF XY:

0.367

AC XY:

26873

AN XY:

73154

show subpopulations

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

show subpopulations

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.:

AF XY:

0.402

AC XY:

291723

AN XY:

726492

show subpopulations

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.:

AF XY:

0.367

AC XY:

26891

AN XY:

73284

show subpopulations

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:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2018	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

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

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