rs2229236

Variant names:

• chrX-1309488-G-A
• rs2229236
• ENST00000355432.8:c.1033G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-1309488-G-A
• chrX-1309488-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172246.4(CSF2RA):​c.1033G>A​(p.Gly345Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,613,916 control chromosomes in the GnomAD database, including 3,001 homozygotes. There are 10,907 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1581 hom., 5644 hem., cov: 33)
  • Exomes 𝑓: 0.0085 (1420 hom. 5263 hem.)
• Consequence: CSF2RA NM_172246.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.02
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006300956).
• BP6: Variant X-1309488-G-A is Benign according to our data. Variant chrX-1309488-G-A is described in ClinVar as Benign. ClinVar VariationId is 178719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172246.4. 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.*9G>A		3_prime_UTR	Exon 13 of 13	NP_758448.1	P15509-1
	CSF2RA	NM_172246.4		c.1033G>A	p.Gly345Arg	missense	Exon 11 of 11	NP_758449.1	P15509-5
	CSF2RA	NM_001161530.2		c.*9G>A		3_prime_UTR	Exon 14 of 14	NP_001155002.1	P15509-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000355432.8	TSL:1	c.1033G>A	p.Gly345Arg	missense	Exon 11 of 11	ENSP00000347606.3	P15509-5
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.*9G>A		3_prime_UTR	Exon 13 of 13	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381524.8	TSL:1	c.*9G>A		3_prime_UTR	Exon 13 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11919 AN: 152156 Hom.: 1573 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.0455

GnomAD2 exomes AF: 0.0206 AC: 5179 AN: 251182 AF XY: 0.0149

Gnomad AFR exome AF: 0.273

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00110

Gnomad OTH exome AF: 0.00897

GnomAD4 exome AF: 0.00849 AC: 12408 AN: 1461642 Hom.: 1420 Cov.: 32 AF XY: 0.00724 AC XY: 5263 AN XY: 727130

African (AFR) AF: 0.283 AC: 9480 AN: 33456

American (AMR) AF: 0.0141 AC: 631 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00930 AC: 243 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000730 AC: 63 AN: 86250

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53420

Middle Eastern (MID) AF: 0.0189 AC: 109 AN: 5762

European-Non Finnish (NFE) AF: 0.000696 AC: 774 AN: 1111830

Other (OTH) AF: 0.0183 AC: 1103 AN: 60378

GnomAD4 genome AF: 0.0785 AC: 11954 AN: 152274 Hom.: 1581 Cov.: 33 AF XY: 0.0758 AC XY: 5644 AN XY: 74466

African (AFR) AF: 0.273 AC: 11342 AN: 41514

American (AMR) AF: 0.0249 AC: 381 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68032

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Bravo AF: 0.0897

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.272 AC: 1198

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.0255 AC: 3100

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_addAF	Benign	-0.93	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0050
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.0
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.028
Sift	Pathogenic	0.0	D
Vest4		0.13
ClinPred		0.0076	T
GERP RS		-0.99

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: rs2229236; hg19: chrX-1428381;