rs73618036

Variant names:

• chrX-1290424-G-A
• rs73618036
• NM_172245.4:c.561G>A

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.561G>A​(p.Thr187Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,613,688 control chromosomes in the GnomAD database, including 318 homozygotes. There are 3,724 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (179 hom., 1880 hem., cov: 32)
  • Exomes 𝑓: 0.0028 (139 hom. 1844 hem.)
• Consequence: CSF2RA NM_172245.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -6.72
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-1290424-G-A is Benign according to our data. Variant chrX-1290424-G-A is described in ClinVar as Benign. ClinVar VariationId is 178716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	NM_172245.4	MANE Select	c.561G>A	p.Thr187Thr	synonymous	Exon 7 of 13	NP_758448.1	P15509-1
	CSF2RA	NM_001161530.2		c.561G>A	p.Thr187Thr	synonymous	Exon 7 of 14	NP_001155002.1	P15509-7
	CSF2RA	NM_001379153.1		c.561G>A	p.Thr187Thr	synonymous	Exon 6 of 13	NP_001366082.1	P15509-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.561G>A	p.Thr187Thr	synonymous	Exon 7 of 13	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.561G>A	p.Thr187Thr	synonymous	Exon 7 of 13	ENSP00000370920.3	P15509-2
	CSF2RA	ENST00000381524.8	TSL:1	c.561G>A	p.Thr187Thr	synonymous	Exon 7 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4047 AN: 152016 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00666 AC: 1674 AN: 251174 AF XY: 0.00503

Gnomad AFR exome AF: 0.0888

Gnomad AMR exome AF: 0.00477

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00283 AC: 4133 AN: 1461556 Hom.: 139 Cov.: 32 AF XY: 0.00254 AC XY: 1844 AN XY: 727078

African (AFR) AF: 0.0942 AC: 3151 AN: 33460

American (AMR) AF: 0.00581 AC: 260 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00833 AC: 48 AN: 5762

European-Non Finnish (NFE) AF: 0.000248 AC: 276 AN: 1111742

Other (OTH) AF: 0.00624 AC: 377 AN: 60378

GnomAD4 genome AF: 0.0267 AC: 4055 AN: 152132 Hom.: 179 Cov.: 32 AF XY: 0.0253 AC XY: 1880 AN XY: 74368

African (AFR) AF: 0.0916 AC: 3800 AN: 41494

American (AMR) AF: 0.0117 AC: 179 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68014

Other (OTH) AF: 0.0128 AC: 27 AN: 2108

Bravo AF: 0.0300

EpiCase AF: 0.000491

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CSF2RA-related disorder (1)
-	-	1	not specified (1)
-	-	1	Surfactant metabolism dysfunction, pulmonary, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.050
DANN	Benign	0.80
PhyloP100		-6.7

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

Other links and lift over

dbSNP: rs73618036; hg19: chrX-1409317; COSMIC: COSV107442037; COSMIC: COSV107442037;