rs181469243

Variant names:

• chrX-1282485-G-A
• rs181469243
• ENST00000432318.8:c.-102G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-1282485-G-A
• chrX-1282485-G-T

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.-102G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 635,396 control chromosomes in the GnomAD database, including 547 homozygotes. There are 4,022 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (418 hom., 2879 hem., cov: 31)
  • Exomes 𝑓: 0.0053 (129 hom. 1143 hem.)
• Consequence: CSF2RA NM_001161529.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42
• 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=-0.56).
• BP6: Variant X-1282485-G-A is Benign according to our data. Variant chrX-1282485-G-A is described in ClinVar as Benign. ClinVar VariationId is 1268410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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.-26-193G>A		intron	N/A	NP_758448.1	P15509-1
	CSF2RA	NM_001161529.2		c.-102G>A		5_prime_UTR	Exon 3 of 14	NP_001155001.1	P15509-1
	CSF2RA	NM_001161530.2		c.-26-193G>A		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.-102G>A		5_prime_UTR	Exon 3 of 14	ENSP00000416437.2	P15509-1
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.-26-193G>A		intron	N/A	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.-26-193G>A		intron	N/A	ENSP00000370920.3	P15509-2

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6187 AN: 151908 Hom.: 418 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.00526 AC: 2541 AN: 483370 Hom.: 129 Cov.: 0 AF XY: 0.00445 AC XY: 1143 AN XY: 257032

African (AFR) AF: 0.135 AC: 1812 AN: 13380

American (AMR) AF: 0.00790 AC: 195 AN: 24692

Ashkenazi Jewish (ASJ) AF: 0.000471 AC: 7 AN: 14874

East Asian (EAS) AF: 0.00127 AC: 40 AN: 31546

South Asian (SAS) AF: 0.00138 AC: 70 AN: 50796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37340

Middle Eastern (MID) AF: 0.00976 AC: 20 AN: 2050

European-Non Finnish (NFE) AF: 0.000504 AC: 142 AN: 281480

Other (OTH) AF: 0.00937 AC: 255 AN: 27212

GnomAD4 genome AF: 0.0407 AC: 6193 AN: 152026 Hom.: 418 Cov.: 31 AF XY: 0.0388 AC XY: 2879 AN XY: 74288

African (AFR) AF: 0.141 AC: 5849 AN: 41442

American (AMR) AF: 0.0141 AC: 215 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5146

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68000

Other (OTH) AF: 0.0280 AC: 59 AN: 2110

Bravo AF: 0.0458

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	-0.56
CADD	Benign	0.080
DANN	Benign	0.86
PhyloP100		-1.4
PromoterAI		-0.025	Neutral

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: rs181469243; hg19: chrX-1401378;