Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000355432.8(CSF2RA):c.1073G>A(p.Arg358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,780 control chromosomes in the GnomAD database, including 195 homozygotes. There are 10,195 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R358L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0091 ( 9 hom., 703 hem., cov: 33)

Exomes 𝑓: 0.012 ( 186 hom. 9492 hem. )

Consequence

CSF2RA
ENST00000355432.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.816

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028986335).

BP6

Variant X-1309528-G-A is Benign according to our data. Variant chrX-1309528-G-A is described in ClinVar as Benign. ClinVar VariationId is 3036043.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00915 (1392/152192) while in subpopulation SAS AF = 0.0324 (156/4822). AF 95% confidence interval is 0.0282. There are 9 homozygotes in GnomAd4. There are 703 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355432.8. 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.*49G>A		3_prime_UTR	Exon 13 of 13	NP_758448.1
CSF2RA	NM_172246.4		c.1073G>A	p.Arg358Gln	missense	Exon 11 of 11	NP_758449.1
CSF2RA	NR_027760.3		n.1296G>A		non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CSF2RA	ENST00000355432.8	TSL:1	c.1073G>A	p.Arg358Gln	missense	Exon 11 of 11	ENSP00000347606.3
CSF2RA	ENST00000486791.6	TSL:1	n.*258G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000436825.1
CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.*49G>A		3_prime_UTR	Exon 13 of 13	ENSP00000370940.3

Frequencies

GnomAD3 genomes

AF:

0.00916

AC:

1393

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.0116

AC:

2901

AN:

251160

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00581

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00924

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0124

AC:

18193

AN:

1461588

Hom.:

186

Cov.:

AF XY:

0.0131

AC XY:

9492

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.00179

AC:

AN:

33472

American (AMR)

AF:

0.00749

AC:

335

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

353

AN:

26132

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0302

AC:

2604

AN:

86246

European-Finnish (FIN)

AF:

0.0105

AC:

562

AN:

53420

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0122

AC:

13562

AN:

1111768

Other (OTH)

AF:

0.0113

AC:

683

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1020

2039

3059

4078

5098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.00915

AC:

1392

AN:

152192

Hom.:

Cov.:

AF XY:

0.00945

AC XY:

703

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00241

AC:

100

AN:

41508

American (AMR)

AF:

0.00935

AC:

143

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.0324

AC:

156

AN:

4822

European-Finnish (FIN)

AF:

0.0104

AC:

110

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0120

AC:

814

AN:

68002

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

140

210

280

350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0135

AC:

ExAC

AF:

0.0121

AC:

1475

EpiCase

AF:

0.00987

EpiControl

AF:

0.0113

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CSF2RA-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.71

(source)

DANN

Benign

0.69

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

PhyloP100

-0.82

PROVEAN

Benign

0.21

REVEL

Benign

0.019

Sift

Pathogenic

0.0

Vest4

0.12

ClinPred

0.0082

GERP RS

-0.69

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.

rs28722602

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