rs140581875

Positions:

• chrX-1288578-A-G
• chrX-1288578-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_172245.4(CSF2RA):​c.279A>G​(p.Thr93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,613,958 control chromosomes in the GnomAD database, including 6 homozygotes. There are 1,060 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T93T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., 123 hem., cov: 32)
  • Exomes 𝑓: 0.0012 (6 hom. 937 hem.)
• Consequence: CSF2RA NM_172245.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.35

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=-1.04).
• BP6: Variant X-1288578-A-G is Benign according to our data. Variant chrX-1288578-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 227279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00154 (235/152294) while in subpopulation AMR AF= 0.00255 (39/15280). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 123 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.279A>G	p.Thr93=	synonymous_variant	5/13	ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.279A>G	p.Thr93=	synonymous_variant	5/13	1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74340

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00162 AC: 406 AN: 251182 Hom.: 0 AF XY: 0.00176 AC XY: 239 AN XY: 135744

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000686

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00154

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00120 AC: 1761 AN: 1461664 Hom.: 6 Cov.: 33 AF XY: 0.00129 AC XY: 937 AN XY: 727140

Gnomad4 AFR exome AF: 0.00164

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000696

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.00100

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00154 AC: 235 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74468

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.00378

Bravo AF: 0.00172

EpiCase AF: 0.00207

EpiControl AF: 0.00308

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 02, 2015

p.Thr93Thr in exon 6 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 0.1% (14/10406) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP 140581875) -

Surfactant metabolism dysfunction, pulmonary, 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.021
DANN	Benign	0.14

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: rs140581875; hg19: chrX-1407471;