rs147124116

chrX-1305655-G-A

Variant summary

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

The ENST00000381509.8(CSF2RA):c.1153G>A(p.Gly385Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,606,370 control chromosomes in the GnomAD database, including 105 homozygotes. There are 1,882 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (63 hom., 1008 hem., cov: 32)
  • Exomes 𝑓: 0.0014 (42 hom. 874 hem.)
• Consequence: CSF2RA ENST00000381509.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27

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=0.0024722815).
• BP6: Variant X-1305655-G-A is Benign according to our data. Variant chrX-1305655-G-A is described in ClinVar as [Benign]. Clinvar id is 178718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.1125+128G>A		intron_variant		ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.1125+128G>A		intron_variant		1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2133 AN: 152158 Hom.: 62 Cov.: 32 AF XY: 0.0135 AC XY: 1005 AN XY: 74340

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00345 AC: 799 AN: 231596 Hom.: 21 AF XY: 0.00251 AC XY: 315 AN XY: 125616

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000389

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.00138 AC: 2008 AN: 1454094 Hom.: 42 Cov.: 32 AF XY: 0.00121 AC XY: 874 AN XY: 722820

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000466

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000199

Gnomad4 OTH exome AF: 0.00301

GnomAD4 genome AF: 0.0140 AC: 2139 AN: 152276 Hom.: 63 Cov.: 32 AF XY: 0.0135 AC XY: 1008 AN XY: 74468

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00803

Bravo AF: 0.0161

ESP6500AA AF: 0.0549 AC: 76

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00448 AC: 542

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Gly385Ser in exon 13B of CSF2RA: This variant is not expected to have clinical s ignificance because it has been identified in 5.5% (76/1384) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs147124116). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	3.5
Dann	Uncertain	0.99
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.29	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PROVEAN	Benign	0.44	N
REVEL	Benign	0.18
Sift	Benign	0.57	T
Sift4G	Benign	0.54	T
Polyphen		1.0	D
Vest4		0.083
MVP		0.42
ClinPred		0.0055	T
GERP RS		0.44

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: rs147124116; hg19: chrX-1424548;