rs147124116

Variant names:

• chrX-1305655-G-A
• rs147124116
• ENST00000381509.8:c.1153G>A

Variant summary

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

The NM_001161531.2(CSF2RA):​c.1153G>A​(p.Gly385Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,606,370 control chromosomes in the GnomAD database, including 105 homozygotes. There are 1,882 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 0.014 (63 hom., 1008 hem., cov: 32)
  • Exomes 𝑓: 0.0014 (42 hom. 874 hem.)
• Consequence: CSF2RA NM_001161531.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27
• 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=0.0024722815).
• BP6: Variant X-1305655-G-A is Benign according to our data. Variant chrX-1305655-G-A is described in ClinVar as Benign. ClinVar VariationId is 178718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161531.2. 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.1125+128G>A		intron	N/A	NP_758448.1	P15509-1
	CSF2RA	NM_001161531.2		c.1153G>A	p.Gly385Ser	missense	Exon 13 of 13	NP_001155003.1	P15509-2
	CSF2RA	NM_001379155.1		c.1153G>A	p.Gly385Ser	missense	Exon 13 of 13	NP_001366084.1	P15509-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000381509.8	TSL:1	c.1153G>A	p.Gly385Ser	missense	Exon 13 of 13	ENSP00000370920.3	P15509-2
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.1125+128G>A		intron	N/A	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381524.8	TSL:1	c.1125+128G>A		intron	N/A	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2133 AN: 152158 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00345 AC: 799 AN: 231596 AF XY: 0.00251

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000389

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.00138 AC: 2008 AN: 1454094 Hom.: 42 Cov.: 32 AF XY: 0.00121 AC XY: 874 AN XY: 722820

African (AFR) AF: 0.0526 AC: 1750 AN: 33270

American (AMR) AF: 0.00106 AC: 45 AN: 42578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39430

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53056

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5750

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1108088

Other (OTH) AF: 0.00301 AC: 181 AN: 60154

GnomAD4 genome AF: 0.0140 AC: 2139 AN: 152276 Hom.: 63 Cov.: 32 AF XY: 0.0135 AC XY: 1008 AN XY: 74468

African (AFR) AF: 0.0500 AC: 2078 AN: 41558

American (AMR) AF: 0.00229 AC: 35 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Bravo AF: 0.0161

ESP6500AA AF: 0.0549 AC: 76

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00448 AC: 542

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.5
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.29	T
PhyloP100		1.3
PROVEAN	Benign	0.44	N
REVEL	Benign	0.18
Sift	Benign	0.57	T
Sift4G	Benign	0.54	T
Polyphen		1.0	D
Vest4		0.083
MVP		0.42
ClinPred		0.0055	T
GERP RS		0.44

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: rs147124116; hg19: chrX-1424548;