rs28733318

Variant names:

• chrX-1282541-A-G
• rs28733318
• ENST00000432318.8:c.-46A>G

Variant summary

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

The NM_001161529.2(CSF2RA):​c.-46A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 747,374 control chromosomes in the GnomAD database, including 4,617 homozygotes. There are 39,899 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (752 hom., 6459 hem., cov: 31)
  • Exomes 𝑓: 0.11 (3865 hom. 33440 hem.)
• Consequence: CSF2RA NM_001161529.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0180
• 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 (BayesDel_noAF=-0.84).
• BP6: Variant X-1282541-A-G is Benign according to our data. Variant chrX-1282541-A-G is described in ClinVar as Benign. ClinVar VariationId is 1265683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161529.2. 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.-26-137A>G		intron	N/A	NP_758448.1	P15509-1
	CSF2RA	NM_001161529.2		c.-46A>G		5_prime_UTR	Exon 3 of 14	NP_001155001.1	P15509-1
	CSF2RA	NM_001161530.2		c.-26-137A>G		intron	N/A	NP_001155002.1	P15509-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000432318.8	TSL:1	c.-46A>G		5_prime_UTR	Exon 3 of 14	ENSP00000416437.2	P15509-1
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.-26-137A>G		intron	N/A	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.-26-137A>G		intron	N/A	ENSP00000370920.3	P15509-2

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12908 AN: 151894 Hom.: 753 Cov.: 31

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.107 AC: 63434 AN: 595362 Hom.: 3865 Cov.: 5 AF XY: 0.104 AC XY: 33440 AN XY: 321414

African (AFR) AF: 0.0224 AC: 382 AN: 17072

American (AMR) AF: 0.189 AC: 7249 AN: 38440

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1358 AN: 19030

East Asian (EAS) AF: 0.0409 AC: 1455 AN: 35578

South Asian (SAS) AF: 0.0792 AC: 5152 AN: 65022

European-Finnish (FIN) AF: 0.149 AC: 7622 AN: 50998

Middle Eastern (MID) AF: 0.105 AC: 283 AN: 2700

European-Non Finnish (NFE) AF: 0.110 AC: 36928 AN: 334856

Other (OTH) AF: 0.0949 AC: 3005 AN: 31666

GnomAD4 genome AF: 0.0849 AC: 12903 AN: 152012 Hom.: 752 Cov.: 31 AF XY: 0.0870 AC XY: 6459 AN XY: 74270

African (AFR) AF: 0.0223 AC: 925 AN: 41520

American (AMR) AF: 0.114 AC: 1744 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5174

South Asian (SAS) AF: 0.0747 AC: 360 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1677 AN: 10550

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7590 AN: 67910

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Bravo AF: 0.0812

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.018
PromoterAI		-0.0022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs28733318; hg19: chrX-1401434;