rs67006588

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_172245.4(CSF2RA):c.50C>G(p.Ala17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 1,613,236 control chromosomes in the GnomAD database, including 15,059 homozygotes. There are 50,831 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 7352 hom., 13897 hem., cov: 31)

Exomes 𝑓: 0.053 ( 7707 hom. 36934 hem. )

Consequence

CSF2RA
NM_172245.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0340

Publications

0 publications found

Variant links:

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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
hereditary pulmonary alveolar proteinosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CSF2RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9688486E-5).

BP6

Variant X-1282753-C-G is Benign according to our data. Variant chrX-1282753-C-G is described in ClinVar as Benign. ClinVar VariationId is 178714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CSF2RA	NM_172245.4	MANE Select	c.50C>G	p.Ala17Gly	missense	Exon 3 of 13	NP_758448.1
CSF2RA	NM_001161530.2		c.50C>G	p.Ala17Gly	missense	Exon 3 of 14	NP_001155002.1
CSF2RA	NM_001379153.1		c.50C>G	p.Ala17Gly	missense	Exon 2 of 13	NP_001366082.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.50C>G	p.Ala17Gly	missense	Exon 3 of 13	ENSP00000370940.3
CSF2RA	ENST00000381509.8	TSL:1	c.50C>G	p.Ala17Gly	missense	Exon 3 of 13	ENSP00000370920.3
CSF2RA	ENST00000381524.8	TSL:1	c.50C>G	p.Ala17Gly	missense	Exon 3 of 13	ENSP00000370935.3

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29461

AN:

151968

Hom.:

7334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0296

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.0782

AC:

19629

AN:

251158

AF XY:

0.0669

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0337

Gnomad EAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0667

GnomAD4 exome

AF:

0.0531

AC:

77589

AN:

1461150

Hom.:

7707

Cov.:

AF XY:

0.0508

AC XY:

36934

AN XY:

726888

show subpopulations

African (AFR)

AF:

0.602

AC:

20142

AN:

33438

American (AMR)

AF:

0.0577

AC:

2581

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

888

AN:

26128

East Asian (EAS)

AF:

0.0201

AC:

796

AN:

39696

South Asian (SAS)

AF:

0.0400

AC:

3450

AN:

86242

European-Finnish (FIN)

AF:

0.0389

AC:

2076

AN:

53418

Middle Eastern (MID)

AF:

0.105

AC:

607

AN:

5760

European-Non Finnish (NFE)

AF:

0.0382

AC:

42454

AN:

1111400

Other (OTH)

AF:

0.0761

AC:

4595

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

3471

6942

10414

13885

17356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1816

3632

5448

7264

9080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.194

AC:

29513

AN:

152086

Hom.:

7352

Cov.:

AF XY:

0.187

AC XY:

13897

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.585

AC:

24242

AN:

41416

American (AMR)

AF:

0.0909

AC:

1387

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3472

East Asian (EAS)

AF:

0.0295

AC:

153

AN:

5186

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4824

European-Finnish (FIN)

AF:

0.0336

AC:

356

AN:

10606

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0393

AC:

2674

AN:

68004

Other (OTH)

AF:

0.155

AC:

326

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

749

1498

2248

2997

3746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.215

TwinsUK

AF:

0.0353

AC:

131

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.575

AC:

2532

ESP6500EA

AF:

0.0417

AC:

358

ExAC

AF:

0.0884

AC:

10735

EpiCase

AF:

0.0413

EpiControl

AF:

0.0408

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CSF2RA-related disorder (1)

not specified (1)

Surfactant metabolism dysfunction, pulmonary, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.21

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.59

MetaRNN

Benign

0.000030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.034

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.19

Sift

Benign

0.11

Sift4G

Uncertain

0.032

Polyphen

0.95

Vest4

0.16

MPC

0.33

ClinPred

0.014

GERP RS

0.19

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.077

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over