X-1282753-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172245.4(CSF2RA):c.50C>G(p.Ala17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 1,613,236 control chromosomes in the GnomAD database, including 15,059 homozygotes. There are 50,831 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (7352 hom., 13897 hem., cov: 31)
  • Exomes 𝑓: 0.053 (7707 hom. 36934 hem.)
• Consequence: CSF2RA NM_172245.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0340

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9688486E-5).
• BP6: Variant X-1282753-C-G is Benign according to our data. Variant chrX-1282753-C-G is described in ClinVar as [Benign]. Clinvar id is 178714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.50C>G	p.Ala17Gly	missense_variant	3/13	ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.50C>G	p.Ala17Gly	missense_variant	3/13	1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29461 AN: 151968 Hom.: 7334 Cov.: 31 AF XY: 0.187 AC XY: 13853 AN XY: 74228

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.0782 AC: 19629 AN: 251158 Hom.: 3180 AF XY: 0.0669 AC XY: 9075 AN XY: 135728

Gnomad AFR exome AF: 0.599

Gnomad AMR exome AF: 0.0532

Gnomad ASJ exome AF: 0.0337

Gnomad EAS exome AF: 0.0280

Gnomad SAS exome AF: 0.0394

Gnomad FIN exome AF: 0.0378

Gnomad NFE exome AF: 0.0420

Gnomad OTH exome AF: 0.0667

GnomAD4 exome AF: 0.0531 AC: 77589 AN: 1461150 Hom.: 7707 Cov.: 31 AF XY: 0.0508 AC XY: 36934 AN XY: 726888

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.0201

Gnomad4 SAS exome AF: 0.0400

Gnomad4 FIN exome AF: 0.0389

Gnomad4 NFE exome AF: 0.0382

Gnomad4 OTH exome AF: 0.0761

GnomAD4 genome AF: 0.194 AC: 29513 AN: 152086 Hom.: 7352 Cov.: 31 AF XY: 0.187 AC XY: 13897 AN XY: 74356

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.0909

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0295

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.155

Bravo AF: 0.215

TwinsUK AF: 0.0353 AC: 131

ALSPAC AF: 0.0355 AC: 137

ESP6500AA AF: 0.575 AC: 2532

ESP6500EA AF: 0.0417 AC: 358

ExAC AF: 0.0884 AC: 10735

EpiCase AF: 0.0413

EpiControl AF: 0.0408

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

Ala17Gly in exon 4 of CSF2RA: This variant is not expected to have clinical sign ificance because it has been identified in 42.5% (1874/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs142270234). -

Surfactant metabolism dysfunction, pulmonary, 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2019

- -

CSF2RA-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 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_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	14
Dann	Benign	0.95
DEOGEN2	Benign	0.21	T;.;T;T;T;.;T;.;.;.
FATHMM_MKL	Benign	0.0067	N
MetaRNN	Benign	0.000030	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L;L;.;L;L;.;L;L;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;.;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.11	T;T;T;T;T;T;.;T;D;T
Sift4G	Uncertain	0.032	D;D;D;D;D;D;D;D;D;D
Polyphen		0.95	P;.;P;.;P;D;.;D;D;D
Vest4		0.16
MPC		0.33
ClinPred		0.014	T
GERP RS		0.19
Varity_R		0.077

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: rs67006588; hg19: chrX-1401646;