rs182764964

Variant names:

• chrX-1285484-G-A
• rs182764964
• NM_172245.4:c.77-294G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172245.4(CSF2RA):​c.77-294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,162 control chromosomes in the GnomAD database, including 3,255 homozygotes. There are 13,940 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3255 hom., 13940 hem., cov: 28)
• Consequence: CSF2RA NM_172245.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.614
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-1285484-G-A is Benign according to our data. Variant chrX-1285484-G-A is described in ClinVar as Benign. ClinVar VariationId is 1235660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 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.77-294G>A		intron	N/A	NP_758448.1	P15509-1
	CSF2RA	NM_001161530.2		c.77-294G>A		intron	N/A	NP_001155002.1	P15509-7
	CSF2RA	NM_001379153.1		c.77-294G>A		intron	N/A	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.77-294G>A		intron	N/A	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.77-294G>A		intron	N/A	ENSP00000370920.3	P15509-2
	CSF2RA	ENST00000381524.8	TSL:1	c.77-294G>A		intron	N/A	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28532 AN: 151042 Hom.: 3254 Cov.: 28

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.214

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 28532 AN: 151162 Hom.: 3255 Cov.: 28 AF XY: 0.189 AC XY: 13940 AN XY: 73806

African (AFR) AF: 0.0579 AC: 2392 AN: 41294

American (AMR) AF: 0.204 AC: 3081 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3462

East Asian (EAS) AF: 0.125 AC: 630 AN: 5044

South Asian (SAS) AF: 0.175 AC: 841 AN: 4794

European-Finnish (FIN) AF: 0.251 AC: 2623 AN: 10448

Middle Eastern (MID) AF: 0.236 AC: 68 AN: 288

European-Non Finnish (NFE) AF: 0.251 AC: 17013 AN: 67710

Other (OTH) AF: 0.213 AC: 447 AN: 2096

Bravo AF: 0.178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.86
PhyloP100		-0.61

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

Other links and lift over

dbSNP: rs182764964; hg19: chrX-1404377;