NM_172245.4:c.491G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_172245.4(CSF2RA):c.491G>A(p.Arg164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00776 in 1,613,084 control chromosomes in the GnomAD database, including 71 homozygotes. There are 6,063 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., 365 hem., cov: 31)

Exomes 𝑓: 0.0080 ( 69 hom. 5698 hem. )

Consequence

CSF2RA
NM_172245.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.243

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=0.014863938).

BP6

Variant X-1290354-G-A is Benign according to our data. Variant chrX-1290354-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00532 (809/151998) while in subpopulation NFE AF = 0.00868 (590/67982). AF 95% confidence interval is 0.0081. There are 2 homozygotes in GnomAd4. There are 365 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RA	NM_172245.4 link	c.491G>A	p.Arg164Gln	missense_variant	Exon 7 of 13	ENST00000381529.9	NP_758448.1	P15509-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9 link	c.491G>A	p.Arg164Gln	missense_variant	Exon 7 of 13	1	NM_172245.4	ENSP00000370940.3		P15509-1

Frequencies

GnomAD3 genomes

AF:

0.00534

AC:

811

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00190

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00868

Gnomad OTH

AF:

0.00480

GnomAD2 exomes

AF:

0.00512

AC:

1285

AN:

251150

AF XY:

0.00497

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.00953

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00249

Gnomad NFE exome

AF:

0.00799

Gnomad OTH exome

AF:

0.00718

GnomAD4 exome

AF:

0.00801

AC:

11705

AN:

1461086

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

5698

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

33470

American (AMR)

AF:

0.00378

AC:

169

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00877

AC:

229

AN:

26124

East Asian (EAS)

AF:

0.000126

AC:

AN:

39694

South Asian (SAS)

AF:

0.00151

AC:

130

AN:

86236

European-Finnish (FIN)

AF:

0.00279

AC:

149

AN:

53420

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00949

AC:

10544

AN:

1111312

Other (OTH)

AF:

0.00689

AC:

416

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

544

1089

1633

2178

2722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.00532

AC:

809

AN:

151998

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

365

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

41474

American (AMR)

AF:

0.00341

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00104

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00190

AC:

AN:

10534

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00868

AC:

590

AN:

67982

Other (OTH)

AF:

0.00475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Bravo

AF:

0.00541

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00768

AC:

ExAC

AF:

0.00471

AC:

572

EpiCase

AF:

0.00780

EpiControl

AF:

0.00723

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg164Gln in exon 8 of CSF2RA: This variant is not expected to have clinical sig nificance because it has been identified in 0.8% (66/8592) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs138964358). -

Surfactant metabolism dysfunction, pulmonary, 4

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.19

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.26

T;.;.;T;T;T;.;.;.;.

FATHMM_MKL

Benign

0.00041

LIST_S2

Benign

0.68

.;T;T;.;T;T;T;T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.015

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

-0.28

N;.;N;N;.;N;N;N;N;N

PhyloP100

-0.24

PrimateAI

Benign

0.45

PROVEAN

Benign

0.39

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.14

T;T;T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.042

D;D;D;D;T;D;T;T;T;D

Polyphen

0.93

P;.;.;P;.;P;D;P;P;P

Vest4

0.12

MVP

0.49

MPC

0.14

ClinPred

0.012

GERP RS

-0.36

Varity_R

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over